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Magnetic nanoparticles used for targeted drug administration present a promising approach in cancer treatment owing to its notable advantages, such as targeted and enhanced encapsulation ability and improved bio protection compared with conventional drug delivery methods. Au shell-iron core nanoparticles (Fe 3 O 4 @Au) were manufactured by a chemical process, coated with dextran to encapsulate curcumin, and functionalized for precision drug delivery using folic acid to combat liver cancer. Dynamic light scattering, scanning electron microscopy, transmission electron microscopy, vibrational spectroscopy, and magnetometry were applied to assess the synthesis of the Fe 3 O 4 @Au-DEX-CU-FA compound. The mean size, zeta potential, and polydispersity of Fe 3 O 4 @Au-DEX-CU-FA were 63.3 ± 2.33 nm, -68.3 ± 1.78 mV, and 0.041 ± 0.008, respectively. Molecular docking models were created to examine the relationship between Fe 3 O 4 @Au-CU and BCL-XL, BAK, and to identify potential binding sites. The loading efficiency and release profile tests examined the medication delivery system's ability. MTT assay was subsequently utilized to determine the optimal dosage and therapeutic efficacy of Fe 3 O 4 @Au-DEX-CU-FA on cancer SNU-449 and healthy THLE-2 cell lines. Flow cytometry demonstrated that Fe 3 O 4 @Au-DEX-CU-FA effectively induced cancer cell death. Fe 3 O 4 @Au-DEX-FA showed a regulated release profile of free curcumin at 37 °C and pH values of 7.4 and 5.4. Real-time PCR revealed increased BAK expression and decreased BCL-XL expression. Nude tumor-bearing mice were used for in vivo experiments. Fe 3 O 4 @Au-DEX-CU-FA treatment dramatically reduced the swelling size compared with free CU and control treatments. It also resulted in a longer lifespan, expanded splenocyte proliferation, increased IFN-γ levels, and decreased IL-4 levels. The regular cells showed no cytotoxic effect compared with the cancer type, confirming that Fe 3 O 4 @Au-DEX-CU-FA maintained its potent anticancer actions. The data suggests that Fe 3 O 4 @Au-DEX-CU-FA possesses a promising potential as a therapeutic agent for combating tumors.

Nuclear pore complexes (NPCs) play a critical role in regulating transport-dependent gene expression, influencing various stages of cancer development and progression. Dysregulation of nucleocytoplasmic transport has profound implications, particularly in the context of cancer-associated protein mislocalization. This review provides specific information about the relationship between nuclear pore complexes, key regulatory proteins, and their impact on cancer biology. Highlighting the influence of tumor-suppressor proteins as well as the potential of gold nanoparticles and intelligent nanosystems in cancer treatment, their role in inhibiting cell invasion is examined. This article concludes with the clinical implications of nuclear export inhibitors, particularly XPO1, as a therapeutic target in various cancers, with selective inhibitors of nuclear export compounds demonstrating efficacy in both hematological and solid malignancies. The review aims to explore the role of NPCs in cancer biology, focusing on their influence on gene expression, cancer progression, protein mislocalization, and the potential of targeted therapies such as nuclear export inhibitors and intelligent nanosystems in cancer treatment. Despite their significance and the number of research studies, the direct role of NPCs in carcinogenesis remains incompletely understood.

Bacteria-infected wounds and antibiotic misuse have become a challenge in the treatment of clinical infections. Therefore, there is an urgent need to design non-antibiotic-dependent multifunctional wound dressings for the treatment of bacterially infected wounds. In this study, an injectable antibacterial hydrogel (pAMPS-Cl/AuNR@HA-DA) based on gold nanorods (AuNR) and N -halamine (pAMPS-Cl) with significant photothermal antibacterial properties was developed. The obtained pAMPS-Cl/AuNR@HA-DA hydrogel showed a sponge-like structure with excellent injectability, self-healing, tissue adhesion, and good hemocompatibility. In addition, the hydrogel exhibited excellent in vitro antibacterial capacity under near-infrared (NIR) laser irradiation through the synergistic action of photothermal therapy (PTT) and chemical release therapy. It also showed an excellent ability to eliminate bacterial infection and promote wound healing, indicating that the pAMPS-Cl/AuNR@HA-DA composite hydrogel could be a promising dressing for the treatment of skin wounds.

Children with extracranial high-risk neuroblastoma (NB) have a poor prognosis due to resistance against apoptosis. Recently, ferroptosis, another form of programmed cell death, has been tested in clinical trials for high-risk NB; however, drug resistance and side effects have also been observed. Here, we find that the gold element in gold nanoclusters can significantly affect iron metabolism and sensitize high-risk NB cells to ferroptosis. Accordingly, we developed a gold nanocluster conjugated with a modified NB-targeting peptide. This gold nanocluster, namely, NANT, shows excellent NB targeting efficiency and dramatically promotes ferroptosis. Surprisingly, this effect is exerted by elevating the noncanonical ferroptosis pathway, which is dependent on heme oxygenase-1-regulated Fe(II) accumulation. Furthermore, NANT dramatically inhibits the growth of high-risk NB in both tumor spheroid and xenograft models by promoting noncanonical ferroptosis evidenced by enhanced intratumoral Fe(II) and heme oxygenase-1. Importantly, this strategy shows excellent cardiosafety, offering a promising strategy to overcome ferroptosis resistance for the efficient and safe treatment of children with high-risk neuroblastoma.

Radiotherapy (RT) is one of the major treatments for cancers and a promising initiator of immune response. Gold nanoparticles are a promising radiosensitizer. In this study, we sought to optimize the drug delivery efficiency of gold nanoparticles and explore their function in delivering stimulator of interferon genes (STING) agonists with or without RT. Gold nanoparticles covalent to MSA-2 (MSA-Au) were mixed with cRGD-modified neutrophil membranes to obtain M-Au@RGD-NM. We explored the treatment efficiency of M-Au@RGD-NM combined with RT. Immune cell regulation and STING pathway activation were detected. We successfully prepared M-Au@RGD-NM with significant tumor suppression by induction of ROS and the resulting DNA damage. In vivo dynamic imaging showed that M-Au@RGD-NM was mainly targeted to radiated tumors. Tumor-bearing mice showed significant tumor inhibition following a combination therapy. M-Au@RGD-NM significantly activated the STING pathway and regulated the whole-body immune response. Locally radiated tumors showed dendritic cells mature, CD8 + T cells upregulation, and M1 polarization, with systematic immune response demonstrated by CD8 + T cell infiltration in abscopal tumors. In this study, we synthesized M-Au@RGD-NM loading MSA-2. Following characterization, we found that RT-based M-Au@RGD-NM treatment achieved good antitumor effects, tumor RT enhancement, and induction of an immune response via STING activation.

Glioma is the most prevalent malignant brain tumor in adults. The development of engineered nanomaterials (ENMs) has led to the emergence of innovative therapeutic strategies for gliomas. Therefore, our aim is to investigate the therapeutic effect of CuO nanoparticles (NPs) on glioma and provide data support for future research. The therapeutic effect of CuO NPs on glioma rats was explored through the detection of inflammatory factors, oxidase, pathological sections, immunofluorescence, neurotransmitter, glioma biomarker proteins and genes, and rat behavioral tests. Additionally, the application prospect of CuO NPs was evaluated by treating U87MG human glioma cell line. In this study, it was found that CuO NPs can alleviate the inflammatory reaction in the hippocampus tissue of glioma rats, promote the production of ·OH and lead to the up-regulation of catalase (CAT) and superoxide dismutase (SOD) enzyme activities. Treatment with CuO NPs also inhibited the expression of matrix metalloproteinase-9 (MMP-9) biomarkers in model rats and glioma cells. Moreover, it enhanced the release of neurotransmitters, which subsequently improved spatial recognition and memory ability of glioma rats. In conclusion, CuO NPs is a potential glioma treatment for ENMs, but still needs modification and modification strategies to improve its biocompatibility and targeted delivery., (© 2024. The Author(s).)

Nanotechnology is an exciting area with great potential for use in biotechnology due to the far-reaching effects of nanoscale materials and their size-dependent characteristics. Silver and other metal nanoparticles have attracted a lot of attention lately because of the exceptional optical, electrical, and antimicrobial characteristics they possess. Silver nanoparticles (AgNPs) stand out due to their cost-effectiveness and abundant presence in the earth's crust, making them a compelling subject for further exploration. The vital efficacy of silver nanoparticles in addressing environmental concerns is emphasized in this thorough overview that dives into their significance in environmental remediation. Leveraging the distinctive properties of AgNPs, such as their antibacterial and catalytic characteristics, innovative solutions for efficient treatment of pollutants are being developed. The review critically examines the transformative potential of silver nanoparticles, exploring their various applications and promising achievements in enhancing environmental remediation techniques. As environmental defenders, this study advocates for intensified investigation and application of silver nanoparticles. Furthermore, this review aims to assist future investigators in developing more cost-effective and efficient innovations involving AgNPs carrying nanoprobes. These nanoprobes have the potential to detect numerous groups of contaminants simultaneously, with a low limit of detection (LOD) and reliable reproducibility. The goal is to utilize these innovations for environmental remediation purposes., Competing Interests: The authors declare that they have no competing interests., (© 2024 Krishna et al.)

The incidence of cancer is increasing and evolving as a major source of mortality. Nanotechnology has garnered considerable scientific interest in recent decades and can offer a promising solution to the challenges encountered with traditional chemotherapy. Nanoparticle utilization holds promise in combating cancer and other diseases, offering exciting prospects for drug delivery systems and medicinal applications. Metallic nanoparticles exhibit remarkable physical and chemical properties, such as their minute size, chemical composition, structure, and extensive surface area, rendering them versatile and cost-effective. Research has demonstrated their significant and beneficial impact on cancer treatment, characterized by enhanced targeting abilities, gene activity suppression, and improved drug delivery efficiency. By incorporating targeting ligands, functionalized metal nanoparticles ensure precise energy deposition within tumors, thereby augmenting treatment accuracy. Moreover, beyond their therapeutic efficacy, metal nanoparticles serve as valuable tools for cancer cell visualization, contributing to diagnostic techniques. Utilizing metal nanoparticles in therapeutic systems allows for simultaneous cancer diagnosis and treatment, while also facilitating controlled drug release, thus revolutionizing cancer care. This narrative review investigates the advancements of metal nanoparticles in cancer treatment, types and mechanisms in targeting cancer cells, application in clinical scenarios, and potential toxicity in medicine., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The overuse of antibiotics has led to the rapid development of multi-drug resistant bacteria, making antibiotics increasingly ineffective against bacterial infections. Consequently, there is an urgent need to develop alternative strategies to combat multi-drug-resistant bacterial infections. In this study, gold nanoparticles modified with ellagic acid (EA-AuNPs) were prepared using a simple and mild one-pot hydrothermal process. EA-AuNPs demonstrated high bactericidal efficacy and broad-spectrum antimicrobial activities against clinical isolates of the antibiotic-resistant ESKAPE pathogens. Furthermore, EA-AuNPs effectively disperse biofilms of multi-drug-resistant bacteria. Additionally, EA-AuNPs mitigated inflammatory responses at the bacterial infection sites. The combined bactericidal and anti-inflammatory treatment with EA-AuNPs resulted in faster curing of peritonitis caused by Staphylococcus aureus in mice compared to treatment with free EA or gentamicin. Moreover, transcriptome analysis revealed that EA-AuNPs exhibited a multi-targeting mechanism, making resistance development in pathogens more challenging than traditional antibiotics that recognize specific cellular targets. Overall, EA-AuNPs emerged as a promising antimicrobial agent against multi-drug-resistant bacterial infections.

Despite its effectiveness in eradicating cancer cells, current tumor radiotherapy often causes irreversible damage to the surrounding healthy tissues. To address this issue and enhance therapeutic outcomes, we developed a multifunctional injectable hydrogel that integrates electromagnetic shielding and magnetothermal effects. This innovation aims to improve the efficacy of brachytherapy while protecting adjacent normal tissues. Recognizing the limitations of existing hydrogel materials in terms of stretchability, durability, and single functionality, we engineered a composite hydrogel by self-assembling nickel nanoparticles on the surface of liquid metal particles and embedding them into an injectable hydrogel matrix. The resulting composite material demonstrates superior electromagnetic interference shielding performance (74.89 dB) and a rapid magnetothermal heating rate (10.9 °C/min), significantly enhancing its in vivo applicability. The experimental results confirm that this innovative nanocomposite hydrogel effectively attenuates electromagnetic waves during brachytherapy, thereby protecting normal tissues surrounding the tumor and enhancing radiotherapy efficacy through magnetothermal therapy. This study advances the safety and effectiveness of cancer treatments and provides new insights into the development of multifunctional biomedical materials, promoting the innovative application of nanotechnology in the medical field.

Nanozymes have been attracting widespread interest for the past decade, especially in the field of cancer therapy, due to their intrinsic catalytic activities, strong stability, and ease of synthesis. However, enhancing their catalytic activity in the tumor microenvironment (TME) remains a major challenge. Herein, we manipulate catalytic activities of Ru nanozymes via modulating lattice spacing in Ru nanocrystals supported on nitrogen-doped carbon support, to achieve improvement in multiple enzyme-like activities that can form cascade catalytic reactions to boost cancer cell killing. In addition, the lattice expansion in Ru nanocrystals improve the responsiveness of the nanozymes to self-powered electric field, achieving maximized cancer therapeutic outcome. Under the electrical stimulation provided by a human self-propelled triboelectric device, the Ru-based nanozyme (Ru1000) with a lattice expansion of 5.99% realizes optimal catalytic performance and cancer therapeutic outcome of breast cancer in female tumor-bearing mice. Through theoretical calculations, we uncover that the lattice expansion and electrical stimulation promote the catalytic reaction, simultaneously, by reducing the electron density and shifting the d-band center of Ru active sites. This work provides opportunities for improving the development of nanozymes., (© 2024. The Author(s).)

Metal ion interference therapy (MIIT) has emerged as a promising approach in the field of nanomedicine for combatting cancer. With advancements in nanotechnology and tumor targeting-related strategies, sophisticated nanoplatforms have emerged to facilitate efficient MIIT in xenografted mouse models. However, the diverse range of metal ions and the intricacies of cellular metabolism have presented challenges in fully understanding this therapeutic approach, thereby impeding its progress. Thus, to address these issues, various amplification strategies focusing on ionic homeostasis and cancer cell metabolism have been devised to enhance MIIT efficacy. In this review, the remarkable progress in Fe, Cu, Ca, and Zn ion interference nanomedicines and understanding their intrinsic mechanism is summarized with particular emphasis on the types of amplification strategies employed to strengthen MIIT. The aim is to inspire an in-depth understanding of MIIT and provide guidance and ideas for the construction of more powerful nanoplatforms. Finally, the related challenges and prospects of this emerging treatment are discussed to pave the way for the next generation of cancer treatments and achieve the desired efficacy in patients.

While tyrosine kinase inhibitor resistance in cancer is a critical issue in the medical field, it is important for clinical testing as well, since it affects the ultimate outcome of cancer therapy. Yet, no effective solutions have been implemented till date. Clinical observations after tyrosine kinase inhibitor treatment reveal that acquired resistance inevitably limits the curative effects of non-small cell lung cancer treatment because of mutations in the epidermal growth factor receptor gene, which are accompanied by epithelial-mesenchymal transition. Here, for the first time, we report that the transmembrane glycoprotein CD44, which is associated with epithelial-mesenchymal transition, chemoresistance, and cancer progression, mediates enhanced endocytosis of iron-platinum alloy nanoparticles (FePt NPs) in the mesenchymal-state gefitinib-resistant (GR+ and M6) cells, via the binding of the CD44 ligand, hyaluronan, to the surface-absorbed hyaluronan-binding protein 2. Upon treatment with FePt NPs, there was higher cellular uptake in mesenchymal-state GR+ and M6 cells, resulting from cell death through ferroptosis and mitochondrial dysfunction, as compared to that observed in the epithelial-state cells. Mechanistically, inactivation of dihydroorotate dehydrogenase elevated the production of mitochondrial lipid peroxidation, and enhanced the cell death in the epithelial-state HCC827 cells, thereby indicating its role in defense against FePt NPs-induced ferroptosis. Furthermore, induction of ferroptosis has been shown to specifically promote the cell death of drug-tolerant "persister" cells and reverse their resistance as well. Therefore, we concluded that FePt NPs preferentially target mesenchymal drug-tolerant "persister" cells and promote ferroptosis, to overcome their resistance. STATEMENT OF SIGNIFICANCE: In the present study, we identified FePt NPs as an innovative agent for cancer treatment, particularly in mesenchymal-state cells that exhibit TKI resistance. Mesenchymal-state cancer cells showed enhanced uptake of FePt NPs via CD44-HA-mediated endocytosis, accompanied by severe cell death and mitochondrial morphology alterations, in comparison to epithelial-state cells. We further elucidated the mechanism underlying FePt NPs-induced ferroptotic cell death as via a burst of mitochondrial LPO and DHODH protein inactivation. In addition, we found that FePt NPs inhibit tumor growth in TKI-resistant mesenchymal GR+ cell-bearing mice with better efficacy than the ferroptotic inducer RSL3. Our current findings on using FePt NPs to overcome TKI resistance through ferroptosis activation may offer a alternative strategy for improved cancer treatment., Competing Interests: Declaration of Competing Interests The authors declare no potential conflicts of interest., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Immune checkpoint blockade (ICB) therapy, while showing promise in various cancers, exhibits limited effectiveness in hepatic carcinoma due to the tumor's immunosuppressive microenvironment (TME) and challenges associated with immune cell infiltration. Efforts to transform the "cold" TME into an "inflamed" state, notably through chemo-immunotherapy, have sparked interest due to their potential to induce immunogenic cell death and augment the infiltration of cytotoxic T lymphocytes (CTLs). Nonetheless, the efficacy of chemo-immunotherapy is often compromised by suboptimal pharmacokinetics, poor tumor accumulation, and off-target toxicity. Herein, in response, we introduce an innovative, milder thermal therapeutic approach leveraging gold nano frameworks with mesopores for the targeted delivery of the immunostimulant imiquimod and NIR-II photothermal therapy. This strategy employs targeted molecule modifications to ensure precise tumor targeting, guided by photoacoustic imaging. Subsequent to mild thermal treatment, there is a release of immunogenic proteins (CRT and HSP90), enhancing tumor immunogenicity. Assisted by imiquimod, substantial CTL infiltration occurs, accompanied by pro-inflammatory factor release (TNF-α, IL-6), transforming M2 macrophages into the M1 phenotype. Ultimately, the proposed strategy combines PD-L1/PD-1 blockade, imiquimod and mild thermal treatment to synergistically enhance tumor immunogenicity, remodel the TME, and restrain hepatic carcinoma, making strides in ICB synergistic immune-thermal therapy.

Background: Breast cancer, with its high morbidity and mortality rates, is a significant global health burden. Traditional treatments-surgery, chemotherapy, and radiotherapy-are widely used but come with drawbacks such as recurrence, metastasis, and significant side effects, including damage to healthy tissues. To address these limitations, new therapeutic strategies are being developed. Peroxidases (POD) can catalyze excess H 2 O 2 in the tumor microenvironment to generate reactive oxygen species (ROS), which induce cancer cell apoptosis by disrupting redox homeostasis and modulating apoptosis-related proteins. However, natural enzymes face challenges like poor stability, high cost, and sensitivity to environmental conditions, limiting their application in breast cancer treatment. Nanozymes, nanomaterials with enzyme-like activity, offer a promising alternative by overcoming these limitations., Methods: In this study, we successfully prepared Au@Pd nanozymes with peroxidase activity by depositing metallic Pd on Au nanoparticles (Au NPs) synthesized using a trisodium citrate reduction method and ascorbic acid reduction. The in vitro validation was conducted through a series of experiments, including ROS detection, flow cytometry, CCK-8 assay, DNA damage assessment, live/dead cell staining, Western blot (WB), and qPCR. Tumor treatment was performed via tail vein injection of the drug, followed by HE staining of the treated tissues and biochemical analysis of the blood., Results: Au@Pd nanozymes can effectively accumulate at the tumor site through the EPR effect and exert peroxidase-like activity, catalyzing the excess H 2 O 2 in the tumor microenvironment to produce ROS. This triggers apoptosis pathways and DNA damage, leading to the downregulation of the anti-apoptotic protein Bcl-2, upregulation of the pro-apoptotic protein Bax, and induction of apoptosis-related genes, demonstrating strong anti-tumor effects., Conclusions: This study developed an efficient nanozyme-mediated catalytic therapy strategy targeting the tumor microenvironment for the treatment of breast cancer cells., (© 2024. The Author(s).)

The global increase in the number of Alzheimer's disease (AD) patients has posed numerous treatment challenges. Six Food and Drug Administration-approved medications (e.g., donepezil and memantine) have demonstrated some efficacy but are primarily used to alleviate symptoms. The etiology of AD is unknown, and the blood-brain barrier restricts drug penetration, which severely restricts the use of various therapeutic agents. With their high targeting, long-lasting effect, and multifunctionality, inorganic nanomaterials provide a novel approach to the treatment of AD. A review of inorganic nanoparticles in the diagnosis and therapy of AD. This paper reviews the research literature on the use of inorganic nanomaterials in the treatment of AD. Gold nanoparticles, superparamagnetic iron oxide nanoparticles, magnetic nanoparticles, carbon nanotubes, and quantum dots are among the inorganic nanomaterials studied. As knowledge of the origins of AD remains limited, the majority of studies on inorganic nanomaterials have primarily focused on interventions on Aβ proteins. Adjusting and enhancing the properties of these inorganic nanomaterials, such as core-shell structure design and surface modification, confer benefits for the treatment of AD. Inorganic nanoparticles have a wide spectrum of therapeutic potential for AD. Despite their potential benefits, however, the safety and translation of inorganic nanomaterials into clinical applications remain formidable obstacles., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

Pseudomonas aeruginosa (PA) is a widely prevalent opportunistic pathogen. Multiple resistant strains of PA have emerged from excessive or inappropriate use of antibiotics, making their eradication increasingly difficult. Therefore, the search for highly efficient and secure novel antimicrobial agents is crucial. According to reports, there is an increasing exploration of nanometals for antibacterial purposes. The antibacterial mechanisms involving the nanomaterials themselves, the release of ions, and the induced oxidative stress causing leakage and damage to biomolecules are widely accepted. Additionally, the study of the cytotoxicity of metal nanoparticles is crucial for their antibacterial applications. This article summarizes the types of metal nanomaterials and metal oxide nanomaterials that can be used against PA, their respective unique antibacterial mechanisms, cytotoxicity, and efforts made to improve antibacterial performance and reduce toxicity, including combination therapy with other materials and antibiotics, as well as green synthesis approaches., (© 2024 Wiley Periodicals LLC.)

Anticancer treatment is performed in various ways, and photothermal therapy (PTT) is gaining traction from a noninvasive treatment perspective. PTT is a treatment technique based on the photothermal effect that kills tumors by increasing their temperature. In this study, gold nanoparticles (AuNPs), which are photothermal agents, were used in numerical simulations to determine the PTT effect by considering diffusion induced changes in the distribution area of the AuNPs. The treatment effect was confirmed by varying the initial injection radius of AuNPs represented by the injection volume, the elapsed time after injection of AuNPs, and the laser intensity. The degree of maintenance of the apoptotic temperature band in the tumor was quantitatively analyzed by the apoptotic variable. Ultimately, if the initial injection radius of AuNPs is 0.7 mm or less, the optimal time to start treatment is 240 min after injection, and for 1.0 and 1.2 mm, it is optimal to start treatment when the elapsed time after injection is 90 and 30 min, respectively. This study identified the optimal treatment conditions for dosage of AuNPs and treatment start time in PTT using AuNPs, which will serve as a reference point for future PTT studies., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

5-Aminolevulinic acid (5-ALA) is a prodrug of porphyrin IX (PpIX). Disadvantages of 5-ALA include poor stability, rapid elimination, poor bioavailability, and weak cell penetration, which greatly reduce the clinical effect of 5-ALA based photodynamic therapy (PDT). Presently, a novel targeting nanosystem was constructed using gold nanoparticles (AuNPs) as carriers loaded with a CSNIDARAC (CC9)-targeting peptide and 5-ALA via Au-sulphur and ionic bonds, respectively, and then wrapped in polylactic glycolic acid (PLGA) NPs via self-assembly to improve the antitumor effects and reduce the side effect. The successful preparation of ALA/CC9@ AuNPs-PLGA NPs was verified using ultraviolet-visible, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The analyses revealed good sphericity with a particle size of approximately140 nm, Zeta potential of 10.11 mV, and slow-controlled release characteristic in a weak acid environment. Confocal microscopy revealed targeting of NCL-H460 cells by NPs by actively internalising CC9 and avoiding the phagocytic action of RAW264.7 cells, and live fluorescence imaging revealed targeting of tumours in tumour-bearing mice. Compared to free 5-ALA, the nanosystem displayed amplified anticancer activity by increasing production of PpIX and reactive oxygen species to induce mitochondrial pathway apoptosis. Antitumor efficacy was consistently observed in three-dimensionally cultured cells as the loss of integrity of tumour balls. More potent anti-tumour efficacy was demonstrated in xenograft tumour models by decreased growth rate and increased tumour apoptosis. Histological analysis showed that this system was not toxic, with lowered liver toxicity of 5-ALA. Thus, ALA/CC9@AuNPs-PLGA NPs deliver 5-ALA via a carrier cascade, with excellent effects on tumour accumulation and PDT through passive enhanced permeability and retention action and active targeting. This innovative strategy for cancer therapy requires more clinical trials before being implemented., Competing Interests: Declaration of competing interest The authors declare that they have no know competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In situ cancer vaccination is an attractive strategy that stimulates protective antitumor immunity. Cytotoxic T lymphocytes (CTLs) are major mediators of the adaptive immune defenses, with critical roles in antitumor immune response and establishing immune memory, and are consequently extremely important for in situ vaccines to generate systemic and lasting antitumor efficacy. However, the dense extracellular matrix and hypoxia in solid tumors severely impede the infiltration and function of CTLs, ultimately compromising the efficacy of in situ cancer vaccines. To address this issue, a robust in situ cancer vaccine, Au@MnO 2 nanoparticles (AMOPs), based on a gold nanoparticle core coated with a manganese dioxide shell is developed. The AMOPs modulated the unfavorable tumor microenvironment (TME) to restore CTLs infiltration and function and efficiently induced immunogenic cell death. The Mn 2+ -mediated stimulator of the interferon genes pathway can be activated to further augment the therapeutic efficacy of the AMOPs. Thus, the AMOPs vaccine successfully elicited long-lasting antitumor immunity to considerably inhibit primary, recurrent, and metastatic tumors. This study not only highlights the importance of revitalizing CTLs efficacy against solid tumors but also makes progress toward overcoming TME barriers for sustained antitumor immunity., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The purpose of current study was to assess the impact of ALA-coated gold nanoclusters (Au NPs) on the combined therapeutic effects of radiotherapy (RT) and photodynamic therapy (PDT) on healthy MCF-10A and MCF-7 breast cancer cells. The Au NPs were covered with ALA using PEG polymer, resulting in the synthesis of Au@ALA NPs. The successful synthesis of the final NPs was confirmed through FTIR, XRD, TEM, and UV-Vis tests. MCF-10A and MCF-7 cell lines were treated with different concentrations of Au@ALA NPs and exposed to irradiation of 2 and 4 Gy (using MV X-ray) and 630 nm laser light irradiation. Cytotoxicity was assessed using a multifaceted approach involving the MTT assay, real-time PCR, and colony forming assay. The findings revealed that the damage inflicted by Au@ALA NPs on cancerous tissue was significantly greater than that on normal tissue. The cytotoxic effects of all experimental groups exhibited a direct correlation with increasing concentrations and radiation doses. The combination of Au@ALA NPs with RT doses of 2 and 4 Gy resulted in a reduction in cell viability by a factor of 1.58 (P = 0.001) and 1.73 (P = 0.004), respectively. Furthermore, the simultaneous intervention of NPs with PDT and RT at doses of 2 and 4 Gy led to a decrease in cell viability by a factor of 2.10 (P = 0.001) and 3.08 (P = 0.001) in turn. Furthermore, the real-time PCR and colonogenic assay results demonstrated that the combined treatment significantly increased phosphorylation of ATM and expression of TP53, indicating an adequate synergistic effect on breast cancer cells. The concurrent application of Au@ALA NPs in RT and PDT successfully enhanced the radiosensitization of breast cancer cells to megavoltage RT and PDT., (© 2024. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

Disturbing cellular redox homeostasis within malignant cells, particularly improving reactive oxygen species (ROS), is one of the effective strategies for cancer therapy. The ROS generation based on nanozymes presents a promising strategy for cancer treatment. However, the therapeutic efficacy is limited due to the insufficient catalytic activity of nanozymes or their high dependence on hydrogen peroxide (H 2 O 2 ) or oxygen. Herein, we reported a nanozyme (CSA) based on well-defined CuSe hollow nanocubes (CS) uniformly covered with Ag nanoparticles (AgNPs) to disturb cellular redox homeostasis and catalyze a cascade of intracellular biochemical reactions to produce ROS for the synergistic therapy of breast cancer. In this system, CSA could interact with the thioredoxin reductase (TrxR) and deplete the tumor microenvironment-activated glutathione (GSH), disrupting the cellular antioxidant defense system and augmenting ROS generation. Besides, CSA possessed high peroxidase-mimicking activity toward H 2 O 2 , leading to the generation of various ROS including hydroxyl radical ( • OH), superoxide radicals ( • O 2 - ), and singlet oxygen ( 1 O 2 ), facilitated by the Cu(II)/Cu(I) redox and H 2 O 2 cycling, and plentiful catalytically active metal sites. Additionally, due to the absorption and charge separation performance of AgNPs, the CSA exhibited excellent photothermal performance in the second near-infrared (NIR-II, 1064 nm) region and enhanced the photocatalytic ROS level in cancer cells. Owing to the inhibition of TrxR activity, GSH depletion, high peroxidase-mimicking activity of CSA, and abundant ROS generation, CSA displays remarkable and specific inhibition of tumor growth.

Designing antibacterial agents with rapid bacterial eradication performance is paramount for the treatment of bacteria-infected wounds. Metal nanoclusters (NCs) with aggregation-induced emission (AIE) have been considered as novel photodynamic antibacterial agents without drug resistance, but they suffer from poor photostability and low charge carrier separation efficiency. Herein, we report the design of a photodynamic antibacterial agent by encapsulating AIE-type AgAu NCs (Ag 28 Au 1 NCs) into a zeolitic Zn(2-methylimidazole) 2 framework (ZIF-8). The encapsulation of AIE-type Ag 28 Au 1 NCs into porous ZIF-8 could not only enhance the photostability of Ag 28 Au 1 NCs by inhibiting their aggregation but also promote the separation of photoinduced charge carriers, resulting in the rapid generation of destructive reactive oxygen species (ROS) for bacterial killing under visible-light irradiation. Consequently, the as-designed photodynamic Ag 28 Au 1 NCs@ZIF-8 antibacterial agent could rapidly eliminate 97.7% of Escherichia coli ( E. coli ) and 91.6% of Staphylococcus aureus ( S. aureus ) within 5 min in vitro under visible light irradiation. Furthermore, in vivo experimental results have highlighted the synergistic effect created by AIE-type Ag 28 Au 1 NCs and ZIF-8, enabling Ag 28 Au 1 NCs@ZIF-8 to effectively eradicate bacteria in infected areas, reduce inflammation, and promote the generation of blood vessels, epithelial tissue, and collagen. This synergistic effect promoted the healing of S. aureus -infected wound, with nearly 100% of wound recovery within 11 days. This work may be interesting because it sheds light on the design of metal NC-based photodynamic nanomedicine for bacteria-infected disease treatment.

Photoimmunotherapy faces challenges due to insufficient intratumoral accumulation of photothermal agents and the reversion of the cancer-immunity cycle during treatment. In this study, an anti-PD-L1-immobilized magnetic gold nanohut, AuNH-2-Ab, with photoresponsive, thermosensitive, and immunomodulatory properties to effectively suppress the growth of primary tumors, elevate immunogenic cell death (ICD) levels, reverse the tumor immune microenvironment (TIME), and consequently inhibit metastases are developed. AuNH-2-Ab achieves high tumor accumulation (9.54% injected dose) following systemic administration, allowing the modulation of hyperthermia dose of over 50 °C in the tumor. By optimizing the hyperthermia dose, AuNH-2-Ab simultaneously target and eliminate cancer cells and tumor-associated macrophages, thereby activating potent antitumor immunity without being compromised by immunosuppressive elements. Hyperthermia/pH induced morphological transformation of AuNH-2-Ab involving the detachment of the surface antibody for in situ PD-L1 inhibition, and exposure of the inner fucoidan layer for natural killer (NK) cell activation. This precision photoimmunotherapy approach reprograms the TIME, significantly prolongs survival in a murine hepatocellular carcinoma model (Hep55.1c), and harnesses the synergistic effects of ICD production and checkpoint inhibitors by utilizing a single nanoplatform., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The management of infected bone defects poses a significant clinical challenge, and current treatment modalities exhibit various limitations. This study focuses on the development of a multifunctional composite scaffold comprising nanohydroxyapatite/polyethyleneglycol diacrylate matrix, silver nanoparticles, graphene oxide (GO), sodium alginate, and M2-type macrophage membrane vesicles (MVs) to enhance the healing of infected bone defects. The composite scaffold demonstrates several key features: first, it releases sufficient quantities of silver ions to effectively eliminate bacteria; second, the controlled release of MVs leads to a notable increase in M2-type macrophages, thereby significantly mitigating the inflammatory response. Additionally, GO acts synergistically with nanohydroxyapatite to enhance osteoinductive activity, thereby fostering bone regeneration. Through meticulous in vitro and in vivo investigations, the composite scaffold exhibits broad-spectrum antimicrobial effects, robust immunomodulatory capabilities, and enhanced osteoinductive activity. This multifaceted composite scaffold presents a promising approach for the sequential treatment of infected bone defects, addressing the antimicrobial, immunomodulatory, and osteogenic aspects. This study introduces innovative perspectives and offers new and effective treatment alternatives for managing infected bone defects., (© 2024 Wiley‐VCH GmbH.)

Cervical cancer (CC) is one of the leading causes of death among women worldwide. The current treatments for this cancer consist of invasive methods such as chemotherapeutic drugs, radiation, immunotherapy and surgery, which could lead to severe side effects and hinder the patient's life quality. Although metal-based therapies, including cisplatin and ruthenium-based compounds, offer promising alternatives, they lack specificity and harm healthy cells. Combining metal nanoparticles with standard approaches has demonstrated remarkable efficacy and safety in the fight against CC. Overall, this review is intended to show the latest advancements and insights into metal-based strategies, creating a promising path for more effective and safer treatments in the battle against CC., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Significance: Multilesional basal cell carcinoma (BCC) are spread on sun exposed skin areas, including arms, face and back. The first-line treatment remains the surgical resection or Mohs surgery. Despite its high complexity, Mohs surgery is well practiced in USA and Germany and presents very good results both in esthetic and in carcinology point of view. Large lesions more than 2 cm remain challenging to remove by topical cream used in photodynamic therapy (PDT). If these larger lesions are not treated in less than 1 month, they could grow deeply in the skin, thus enhancing the risk of reoccurrence and the severity of the disease. Despite this model herein studied, that is non melanoma skin cancer is a good prognostic cancer, the therapy aims to be applied to more aggressive melanoma skin cancers., Aim: Total regression of large cutaneous lesions less than 1 month with no reoccurrence., Approach: Tumor induction on murine model bearing a 500 mm 3 subcutaneous lesion. Increasing dose of gold nanoparticles at fixed initial concentration C0 = 0.3 mg/mL, infused into the tumor then exposition of the region of interest to NIR medical laser to assess the therapy. One or two intratumoral administration(s) were compared to surgery and control, that is no treatment, laser alone or nanoparticles alone., Results: Gold nanoparticles alone or the NIR laser alone did not induce the tumor regression. The combination of laser and nanoparticles called plasmonic nanophotothermal therapy induced apoptosis. Derma and hypoderm do not show any visible gold nanoparticles and demonstrated a good cicatrization process., Conclusion: Plasmonic nanophotothermal therapy using two doses of gold nanoparticles was the only protocol that proved its efficacy on large lesions in 14 days, that is 500 mm 3 on a murine model bearing human basal cell carcinoma., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Objective: Pulp regeneration with bioactive dentin-pulp complex has been a research hotspot in recent years. Stem cell therapy provided an interest strategy to regenerate the dental-pulp complex. Hence, this study aimed to evaluate the effects of photosensitive gelatin methacrylate (GelMA) hydrogel encapsulating dental pulp stem cells (DPSCs) and silver nanoparticles (AgNPs) for dental pulp regeneration in vitro., Methods: First, the AgNPs@GelMA hydrogels were prepared by lithium phenyl-2,4,6-trimethyl-benzoyl phosphinate (LAP) initiation via blue-light emitting diode light. The physical and chemical properties of AgNPs@GelMA hydrogels were comprehensively analysed via scanning electron microscopy (SEM), and mechanical characterisation, such as swelling ability, degradation properties, and AgNP release profile. Then, AgNPs@GelMA hydrogels encapsulated DPSCs were used to establish an AgNPs@GelMA biomimetic complex, further analysing its biocompatibility, antibacterial properties, and angiogenic capacity in vitro., Results: The results indicated that GelMA hydrogels demontrated optimal characteristics with a monomer:LAP ratio of 16:1. The physico-chemical properties of AgNPs@GelMA hydrogels did not change significantly after loading with AgNPs. There was no significant difference in AgNP release rate amongst different concentrations of AgNPs@GelMA hydrogels. Fifty to 200 μg/mL AgNPs@GelMA hydrogels could disperse E faecalis biofilm and reduce its metabolic activity . Furthermore, cell proliferation was arrested in 100 and 200 μg/mL AgNPs@GelMA hydrogels. The inhibition of 50 μg/mL AgNPs@GelMA hydrogels on E faecalis biofilm was above 50%, and the cell viability of the hydrogels was higher than 90%. The angiogenesis assay indicated that AgNPs@GelMA hydrogels encapsulating DPSCs could induce the formation of capillary-like structures and express angiogenic markers CD31, vascular endothelial growth factor , and von willebrand factor (vWF) in vitro., Conclusions: Results of this study indicate that 50 μg/mL AgNPs@GelMA hydrogels encapsulating DPSCs had significant antibacterial properties and angiogenic capacity, which could provide a significant experimental basis for the regeneration of the dentin-pulp complex., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic wounds of significant severity and acute injuries are highly vulnerable to fungal infections, drastically impeding the expected wound healing trajectory. The clinical use of antifungal therapeutic drug is hampered by poor solubility, high toxicity and adverse reactions, thereby necessitating the urgent development of novel antifungal therapy strategy. Herein, this study proposes a new strategy to enhance the bioactivity of small-molecule antifungal drugs based on multifunctional metal nanozyme engineering, using amphotericin B (AmB) as an example. AmB-decorated gold nanoparticles (AmB@AuNPs) are synthesized by a facile one-pot reaction strategy, and the AmB@AuNPs exhibit superior peroxidase (POD)-like enzyme activity, with maximal reaction rates (V max ) 3.4 times higher than that of AuNPs for the catalytic reaction of H 2 O 2 . Importantly, the enzyme-like activity of AuNPs significantly enhanced the antifungal properties of AmB, and the minimum inhibitory concentrations of AmB@AuNPs against Candida albicans (C. albicans) and Saccharomyces cerevisiae (S. cerevisiae) W303 are reduced by 1.6-fold and 50-fold, respectively, as compared with AmB alone. Concurrent in vivo studies conducted on fungal-infected wounds in mice underscored the fundamentally superior antifungal ability and biosafety of AmB@AuNPs. The proposed strategy of engineering antifungal drugs with nanozymes has great potential for enhanced therapy of fungal infections and related diseases., (© 2024 Wiley‐VCH GmbH.)

Cancer immunotherapy remains a significant challenge due to insufficient proliferation of immune cells and the sturdy immunosuppressive tumor microenvironment. Herein, we proposed the hypothesis of cuproptosis-lactate regulation to provoke cuproptosis and enhance anti-tumor immunity. For this purpose, copper-human serum albumin nanocomplex loaded gold nanocages with bacterial membrane coating (BAu-CuNCs) were developed. The targeted delivery and disassembly of BAu-CuNCs in tumor cells initiated a cascade of reactions. Under near infrared (NIR) laser irradiation, the release of copper-human serum albumin (Cu-HSA) was enhanced that reacted with intratumoral glutathione (GSH) via a disulfide exchange reaction to liberate Cu 2+ ions and exert cuproptosis. Subsequently, the cuproptosis effect triggered immunogenic cell death (ICD) in tumor by the release of damage associated molecular patterns (DAMPs) to realize anti-tumor immunity via robust production of cytotoxic T cells (CD8 + ) and helper T cells (CD4 + ). Meanwhile, under NIR irradiation, gold nanocages (AuNCs) promoted excessive reactive oxygen species (ROS) generation that played a primary role in inhibiting glycolysis, reducing the lactate and ATP level. The combine action of lower lactate level, ATP reduction and GSH depletion further sensitized the tumor cells to cuproptosis. Also, the lower lactate production led to the significant blockage of immunosuppressive T regulatory cells (Tregs) and boosted the anti-tumor immunity. Additionally, the effective inhibition of breast cancer metastasis to the lungs enhanced the anti-tumor therapeutic impact of BAu-CuNCs + NIR treatment. Hence, BAu-CuNCs + NIR concurrently induced cuproptosis, ICD and hindered lactate production, leading to the inhibition of tumor growth, remodeling of the immunosuppressive tumor microenvironment and suppression of lung metastasis. Therefore, leveraging cuproptosis-lactate regulation, this approach presents a novel strategy for enhanced tumor immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests that could influence the work stated in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Breast cancer remains a formidable challenge in oncology despite significant advancements in treatment modalities. Conventional therapies such as surgery, chemotherapy, radiation therapy, and hormonal therapy have been the mainstay in managing breast cancer for decades. However, a subset of patient's experiences treatment failure, leading to disease recurrence and progression. Therefore, this study investigates the therapeutic potential of green-synthesized silver nanoparticles (AgNPs) using an African medicinal plant (Dicoma anomala methanol root extract) as a reducing agent for combating breast cancer. AgNPs were synthesized using the bottom-up approach and later modified with liposomes (Lip) loaded with photosensitizer (PS) zinc phthalocyanine tetrasulfonate (Lip@ZnPcS 4 ) using thin film hydration method. The successful formation and Lip modification of AgNPs, alongside ZnPcS 4 , were confirmed through various analytical techniques including UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), high-resolution transmission electron microscopy (HR-TEM), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Following a 24 h treatment period, MCF-7 cells were assessed for viability using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT viability assay), cell death analysis using mitochondrial membrane potential (MMP) (ΔΨm), Annexin V-fluorescein isothiocyanate (FITC)-propidium iodide (PI) kit, and caspase- 3, 8 and 9 activities. The experiments were repeated four times (n = 4), and the results were analyzed using SPSS statistical software version 27, with a confidence interval set at 0.95. The synthesized nanoparticles and nanocomplex, including AgNPs, AgNPs-Lip, Lip@ZnPcS 4 , and AgNPs-Lip@ZnPcS 4 , exhibited notable cytotoxicity and therapeutic efficacy against MCF-7 breast cancer cells. Notably, the induction of apoptosis, governed by the upregulation of apoptotic proteins i.e., caspase 8 and 9 activities. In addition, caspase 3 was not expressed by MCF-7 cells in both control and experimental groups. Given the challenging prognosis associated with breast cancer, the findings underscore the promise of liposomal nanoformulations in cancer photodynamic therapy (PDT), thus warranting further exploration in clinical settings., Competing Interests: Declaration of competing interest Authors declare no competing interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Gelling-fibre dressings have been found to be a rapid and effective tool for exudate management. Suprasorb Liquacel Pro is a soft, conformable non-woven dressing made from sodium carboxymethyl cellulose and strengthening cellulose fibres. When it comes into contact with wound exudate or blood, the absorbent dressing forms a gel, creating a moist wound environment. Cell debris and bacteria in the exudate are retained inside the fibre dressing and removed during the dressing change. The high vertical absorption of exudate into the fibre dressing protects the wound environment and the wound edge, thus supporting the healing process. Suprasorb Liquacel Ag has additional antimicrobial abilities with the inclusion of nanosilver technology, shown to be effective in killing bacteria and managing bioburden.

Background: Suprasorb Liquacel Pro (standard test dressing) and Suprasorb Liquacel Ag (test dressing with silver nanoparticles) are absorptive gelling-fibre dressings designed to manage wound exudate levels and promote moist wound healing, with the latter having additional antimicrobial properties., Aims: To assess the impact of the test dressing on healing, exudate levels and signs of infection., Methods: Patients with moderately-to-highly exuding hard-to-heal wounds of any type were dressed with the standard test dressing or the test dressing with silver nanoparticles if they showed covert or overt signs of local infection. Comparative data were collected at baseline and 4-week conclusion. Adverse events and patient and professional opinions were also reported and collated., Findings: There were 19 patients with lower-limb wounds of various types present for a mean of 26 months. At baseline, most wounds were deteriorating or static (68%), while at conclusion most were improving or healed (84%), with additional indicators of improved healing. The number of patients with moderate-to-high exudate levels decreased from 84% to 53%. The 15 patients using the test dressing with silver nanoparticles saw reductions in covert signs of infection from 93% to 80%, overt signs of infection from 33% to 13% and antibiotic use from 13% to 7%., Conclusions: On average, the test dressings were effective in managing and reducing the barriers to healing, including high exudate, infection and biofilm, and in restarting stalled healing.

Patients suffering from diabetes mellitus are prone to develop diabetic wounds that are non-treatable with conventional therapies. Hence, there is an urgent need of hour to develop the therapy that will overcome the lacunas of conventional therapies. This investigation reports the Quality by Design-guided one-pot green synthesis of unique Opto-Laser activatable nanoSilver ThermoGel (OL→nSil-ThermoGel) for hyperthermia-assisted treatment of full-thickness diabetic wounds in mice models. The characterization findings confirmed the formation of spherical-shaped nanometric Opto-Laser activatable nanoSilver (30.75 ± 2.7 nm; ∆T: 37 ± 0.2 °C → 66.2 ± 0.1 °C; at 1.8 W/cm 2 NIR laser density). The findings indicated acceptable in vitro cytocompatibility and significant keratinocyte migration (95.04 ± 0.07 %) activity of OL→nSil towards HaCaT cells. The rheological data of OL→nSil hybridized in situ thermoresponsive gel (OL→nSil-ThermoGel) showed the gelling temperature at 32 ± 2 °C. In vivo studies on full-thickness diabetic wounds in a Mouse model showed OL→nSil-ThermoGel accelerated wound closure (94.42 ± 1.03 %) and increased collagen synthesis, angiogenesis, and decreased inflammatory markers. Similarly, immunohistochemistry study showed significant angiogenesis and faster phenotypic switching of fibroblasts to myofibroblasts in OL→nSil-ThermoGel treated diabetic wounds. Histological evaluation revealed a marked rise in keratinocyte migration, organized collagen deposition, and early regeneration of the epithelial layer compared to the diabetic wound control. In conclusion, the OL→nSil-ThermoGel modulates the cytokines, re-epithelialization, protein expression, and growth factors, thereby improving the repair and regeneration of diabetic wounds in mice., Competing Interests: Declaration of competing interest The authors declare the conflict of interest. The work described in this manuscript has been filed for an Indian patent at the Indian Patent Office (IPO), Mumbai, India; Application No.: 202321049846; Date of Application: 24/07/2023., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cisplatin (DDP) is a prevalent chemotherapeutic agent used in tumor therapy, yet DDP-induced acute kidney injury (AKI) severely limits its clinical application. Antioxidants as reactive oxygen species (ROS) scavengers can circumvent this adverse effect while leading to the decrease of efficacy to tumor. Herein, we report ultrasmall ruthenium nanoparticles (URNPs) as switchable ROS scavengers/generators to alleviate DDP-induced AKI and improve its therapeutic efficacy. In the physiological environment of the kidney, URNPs mimic multi-enzyme activities, such as superoxide dismutase and catalase, effectively protecting the renal cell and tissue by down-regulating the increased ROS level caused by DDP and alleviating AKI. Specifically, URNPs are oxidized by high levels of H 2 O 2 in the tumor microenvironment (TME), resulting in the generation of oxygen vacancies and Ru 3+ /Ru 4+ ions. This unique structure transformation endows URNPs to generate singlet oxygen ( 1 O 2 ) under laser irradiation and hydroxyl radicals (∙OH) through a Fenton-like reaction in tumor cell and tissue. The simultaneous generation of multifarious ROS effectively improves the efficacy of DDP in vitro and in vivo. This TME-responsive ROS scavenger/generator acts as an adjuvant therapeutic agent to minimize side effects and improve the efficacy of chemotherapy drugs, providing a new avenue to chemotherapy and facilitating clinical tumor therapy., (© 2024. The Author(s).)

Bacterial infection has always posed a severe threat to public health. Gold nanoparticles (Au NPs) exhibit exceptional biocompatibility and hold immense potential in biomedical applications. However, their antibacterial effectiveness is currently unsatisfactory. Herein, a chiral antibacterial agent with high stability was prepared by the modification of Au NPs with d-cysteine with the assistance of polyethylene glycol (PEG). The as-synthesized d-cysteine/PEG-Au NPs (D/P-Au NPs) exhibited a stronger (99.5-99.9%) and more stable (at least 14 days) antibacterial performance against Gram-negative ( Escherichia coli and Listeria monocytogenes ) and Gram-positive ( Salmonella enteritidis and Staphylococcus aureus ) bacteria, compared with other groups. The analysis of the antibacterial mechanism revealed that the D/P-Au NPs mainly affected the assembly of ribosomes, the biosynthesis of amino acids and proteins, as well as the DNA replication and mismatch repair, ultimately leading to bacterial death, which is significantly different from the mechanism of reactive oxygen species-activated metallic antibacterial NPs. In particular, the D/P-Au NPs were shown to effectively accelerate the healing of S. aureus -infected wounds in mice to a rate comparable to or slightly higher than that of vancomycin. This work provides a novel approach to effectively design chiral antibacterial agents for bacterial infection treatment.

Melanoma is the most invasive and lethal form of skin cancer that arises from the malignant transformation of specialized pigment-producing cell melanocytes. Nanomedicine represents an important prospect to mitigate the difficulties and provide significant benefits to cure melanoma. In the present study, we investigated in vitro and in vivo therapeutic efficacies of copper nitroprusside analogue nanoparticles (abbreviated as CuNPANP) towards melanoma. Initially, in vitro anti-cancer activities of CuNPANP towards melanoma cells (B16F10) were evaluated by several experiments such as [methyl-3H]-thymidine incorporation assay, cell cycle and apoptosis assays using FACS analysis, ROS generation using DCFDA, DHE and DAF2A reagents, internalization of nanoparticles through ICP-OES analysis, co-localization of the nanoparticles using confocal microscopy, JC-1 staining to investigate the mitochondrial membrane potential (MMP) and immunofluorescence studies to analyze the expressions of cytochrome-c, Ki-67, E-cadherin as well as phalloidin staining to analyze the cytoskeletal integrity. Further, the in vivo therapeutic effectiveness of the nanoparticles was established towards malignant melanoma by inoculating B16F10 cells in the dorsal right abdomen of C57BL/6J mice. The intraperitoneal administration of CuNPANP inhibited tumor growth and increased the survivability of melanoma mice. The in vivo immunofluorescence studies (Ki-67, CD-31, and E-cadherin) and TUNEL assay further support the anti-cancer and apoptosis-inducing potential of CuNPANP, respectively. Finally, various signaling pathways and molecular mechanisms involved in anti-cancer activities were further evaluated by Western blot analysis. The results altogether indicated the potential use of copper-based nanomedicines for the treatment of malignant melanoma.

The healing of a wound under tension (hereafter, "tension wound") often coincides with the development of hypertrophic scars in clinical settings. Currently, compress bandages offer a potential alternative for the healing of tension wounds; however, their application in surgery is limited due to their prefabricated patch form. To overcome this, a tension-shielding hydrogel system was designed using photocurable catechol-grafted hyaluronic acid and tannic-acid silver nanoparticles (hereafter, "HTA system"). The hydrogel exhibited tension-shielding capacity, reducing wound tension via shape-fixation and ultimately reducing scar formation. The HTA hydrogel exhibited superior photothermal antibacterial efficacy, self-healing properties, and effective dissipation of energy, thereby promoting tissue regeneration. The hydrogel significantly inhibited the mechanotransduction pathway, thus preventing Engrailed-1 activation and reducing the fibrotic response. The HTA hydrogel system, therefore, provides a treatment strategy for tension wounds, burn wounds and other wounds that are prone to form hypertrophic scars via creating a tension-free local environment. STATEMENT OF SIGNIFICANCE: In our study, we presented a wound-dressing hydrogel system (HTA) that exhibit shape-fixing capacity in tension wound model. Here, we designed and modified a tension regulator, applied it to mice, and furthermore, established a tension wound model in mice with adjustable tension. Outcomes showed that the HTA hydrogel system can effectively form a shape-fixed environment on tension wounds and dynamic wounds, thus promoting scarless healing. Additionally, HTA performs injectability, rapid crosslinking, biocompatibility, wet adhesion, hemostasis and photothermal antibacterial properties. We believe this research has various potential clinical applications, including scarless-healing in tension wounds, treatment of acute bleeding, treatment of infected wounds, and even internal organ repair., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Trichinella spiralis infection is a food-borne zoonotic disease caused by nematodes that dwell in the tissues, presenting a significant public health concern. This study aimed to evaluate the effectiveness of different treatments including silver nanoparticles (AgNPs), myrrh biosynthesized AgNPs "AgNPs synthesized using plant-based green technologies", myrrh extract, and myrrh essential oil, as alternative treatments against T. spiralis infection. Parasitological, histopathological, and cytotoxicity assessments were conducted to investigate the effects of various concentrations of these treatments in reducing the populations of adult worms and larvae during both the intestinal and muscular phases of T. spiralis-infected mice. The results showed that the highest antihelminthic efficacy against the intestinal phase of T. spiralis was achieved by myrrh extract (86.66%), followed closely by AgNPs (84.96%) and myrrh AgNPs (82.51%) at higher concentrations (800 mg/kg for myrrh extract, 40 μg/mL for AgNPs, and 40 μg/mL for myrrh AgNPs). While the group treated with myrrh essential oil showed the lowest percentage of adult reduction (78.14%). However, all treatments demonstrated comparable effects in reducing the larvae population in the muscle phase. Histopathological examination of the tissues revealed compelling evidence of the effectiveness of AgNPs, particularly when prepared with myrrh. Additionally, a comprehensive assessment of the cytotoxicity of AgNPs indicated low toxicity levels. This study supports that AgNPs synthesized using plant-based green technologies hold therapeutic potential for the treatment of T. spiralis infection. These findings present a promising avenue for the development of novel antiparasitic drugs that are both effective and safe. RESEARCH HIGHLIGHTS: Myrrh extract has the highest antihelminthic efficacy against the intestinal phase of T. spiralis. Histopathological examination of the tissues revealed compelling evidence of the effectiveness of AgNPs, particularly when prepared with myrrh. During intestinal phase of T. spiralis, varying levels of nanoparticle precipitation were detected in the liver, brain, lung, and intestine. During the muscular phase, the highest amount of AgNPs precipitation was detected in the liver, followed by the brain, and lung., (© 2024 Wiley Periodicals LLC.)

To overcome current limitations in photoimmunotherapy, such as insufficient tumor antigen generation and a subdued immune response, a novel photo-/metallo dual-mode immunotherapeutic agent (PMIA) is introduced for potent near-infrared (NIR) light-triggered cancer therapy. PMIA features a dumbbell-like AuPt heterostructure decorated with starry Pt nanoclusters, meticulously engineered for enhancing plasmonic catalysis through multi-dimensional regulation of Pt growth on Au nanorods. Under NIR laser exposure, end-tipped Pt nanoclusters induce efficient electron-hole spatial separation along the longitudinal axis, resulting in radial and axial electron distribution polarization, conferring unique anisotropic properties to PMIA. Additionally, starry Pt nanoclusters on the sides of Au nanorods augment the local electron enrichment field. Validated through finite-difference time-domain analysis and Raman scattering, this configuration fosters local electron enrichment, facilitating robust reactive oxygen species generation for potent photoimmunotherapy. Moreover, Pt nanoclusters facilitate Pt 2+ ion release, instigating intranuclear DNA damage and inducing synergistic immunogenic cell death (ICD) for metalloimmunotherapy. Consequently, PMIA elicits abundant danger-associated molecular patterns, promotes T cell infiltration, and triggers systemic immune responses, effectively treating primary and distant tumors, inhibiting metastasis in vivo. This study unveils a pioneering dual-mode ICD amplification strategy driven by NIR light, synergistically integrating photoimmunotherapy and metalloimmunotherapy, culminating in potent cancer photometalloimmunotherapy., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Cells can sense the mechanical stimulation of nanoparticles (NPs) and then regulate the cellular uptake process. The enhanced endocytosis efficiency can improve the concentration of NPs in tumor cells significantly, which is the key prerequisite for achieving efficient biological performance. However, the preparation methods of NPs with flexible and tunable stiffness are relatively limited, and the impact of stiffness property on their interaction with tumor cells remains unclear. In this study, soft liquid metal (LM) core was coated with hard silica layer, the obtained core-shell NPs with a wide range of Young's modulus (130.5 ± 25.6 MPa - 1729.2 ± 146.7 MPa) were prepared by adjusting the amount of silica. It was found that the NPs with higher stiffness exhibited superior cellular uptake efficiency and lysosomal escape ability compared to the NPs with lower stiffness. The silica layer not only affected the stiffness, but also improved the photothermal stability of the LM NPs. Both in vitro and in vivo results demonstrated that the NPs with higher stiffness displayed significantly enhanced tumor hyperthermia capability. This work may provide a paradigm for the preparation of NPs with varying stiffness and offer insights into the role of the mechanical property of NPs in their delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acute pancreatitis (AP) is a common and serious acute inflammatory disease with high severity rate and mortality. Inflammation and oxidative stress play an extremely important role in the development of AP disease. Polyvinylpyrrolidone-modified iridium nanoparticles (IrNP-PVP) have multienzyme mimetic activity, and the aim of this article is to discuss the therapeutic alleviative effects of the ultrasmall nanozymes IrNP-PVP on AP through their antioxidant and anti-inflammatory effects. IrNP-PVP were proved to inhibit inflammation and scavenge reactive oxygen species (ROS) at the cellular level. The synthetic IrNP-PVP exhibit remarkable antioxidant and anti-inflammatory activities in the prevention and treatment of AP mice by establishing murine AP model, which can reduce the oxidative stress and inflammatory response. The results of this article indicated that the ultrasmall nanozymes IrNP-PVP effectively alleviate AP via scavenging ROS as well as suppressing inflammation both in vivo and in vitro, which might provide enormous promise for the AP management., (© 2024 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Photodynamic therapy (PDT) is a minimally invasive cancer treatment that, despite its significant attention, faces limitations in penetration depth, which restrict its effectiveness. Herein, it is found that gold nanobipyramid (AuNBs) coated with TiO 2 can form a core-shell heterogeneous structure (AuNBs@TiO 2 ) with strong absorption at second near infrared (NIR-II) region. A substantial quantity of reactive oxygen species (ROS), including singlet oxygen ( 1 O 2 ), superoxide anion radicals, and hydroxyl radicals, can be rapidly generated when subjecting the AuNBs@TiO 2 aqueous suspension to 1064 nm laser irradiation. The quantum yield for sensitization of 1 O 2 by AuNBs@TiO 2 is 0.36 at 1064 nm light excitation. In addition, the Au element as high-Z atoms in the nanosystem can improve the ability of computed tomographic (CT) imaging. As compared to commercial iohexol, the AuNBs@TiO 2 nanoparticle exhibits significantly better CT imaging effect, which can be used to guide PDT. In addition, the nano-photosensitizer shows a remarkable therapeutic effect against established solid tumors and prevents tumor metastasis and potentiates immune checkpoint blockade therapy. More importantly, here the great potentials of AuNBs@TiO 2 are highlighted as a theranostic platform for CT-guided cancer photodynamic immunotherapy., (© 2024 Wiley‐VCH GmbH.)

Cisplatin chemoradiotherapy (CRT) is the established standard of care for managing locally advanced human papillomavirus-positive head/neck carcinoma. The typically young patients may suffer serious and long-time side effects caused by the treatment, such as dysphagia, and hearing loss. Thus, ensuring a satisfactory post-treatment quality of life is paramount. One potential replacing approach to the classical CRT involves the combination of standard-dose radiotherapy and radiosensitizers such as noble metal nanoparticles (NPs). However, several concerns about size, shape, and biocompatibility limit the translation of metal nanomaterials to the clinical practice. Here, it is demonstrated that a new model of nonpersistent gold nanoarchitectures containing cisplatin (NAs-Cluster-CisPt) generates, in combination with radiotherapy, a significant in vivo tumor-reducing effect compared to the standard CRT, achieving a complete tumor clearance in 25% of the immunocompetent models that persist for 60 days. These findings, together with the negligible amount of metals recognized in the excretory organs, highlight that the concurrent administration of NAs-Cluster-CisPt and radiotherapy has the potential to overcome some clinical limitations associated to NP-based approaches while enhancing the treatment outcome with respect to standard CRT. Overall, despite further mechanistic investigations being essential, these data support the exploiting of nonpersistent metal-nanomaterial-mediated approaches for oral cancer management., (© 2024 Wiley‐VCH GmbH.)

The prevalence of major bacterial infections has emerged as a significant menace to human health and life. Conventional treatment methods primarily rely on antibiotic therapy, but the overuse of these drugs has led to a decline in their efficacy. Moreover, bacteria have developed resistance towards antibiotics, giving rise to the emergence of superbugs. Consequently, there is an urgent need for novel antibacterial agents or alternative strategies to combat bacterial infections. Nanoantibiotics encompass a class of nano-antibacterial materials that possess inherent antimicrobial activity or can serve as carriers to enhance drug delivery efficiency and safety. In recent years, metal nanoclusters (M NCs) have gained prominence in the field of nanoantibiotics due to their ultra-small size (less than 3 nm) and distinctive electronic and optical properties, as well as their biosafety features. In this review, we discuss the recent progress of M NCs as a new generation of antibacterial agents. First, the main synthesis methods and characteristics of M NCs are presented. Then, we focus on reviewing various strategies for detecting and treating pathogenic bacterial infections using M NCs, summarizing the antibacterial effects of these nanoantibiotics on wound infections, biofilms, and oral infections. Finally, we propose a perspective on the remaining challenges and future developments of M NCs for bacterial infectious therapy.

A better understanding of the molecular and cellular events involved in the inflammation process has opened novel perspectives in the treatment of inflammatory diseases, particularly through the development of well-designed nanomedicines. Here we describe the design of a novel class of anti-inflammatory nanomedicine (denoted as Au@MIL) synthesized through a one-pot, cost-effective and green approach by coupling a benchmark mesoporous iron(III) carboxylate metal organic framework (MOF) ( i.e. MIL-100(Fe)) and glutathionate protected gold nanoclusters ( i.e. Au 25 SG 18 NCs). This nano-carrier exhibits low toxicity and excellent colloidal stability combined with the high loading capacity of the glucocorticoid dexamethasone phosphate (DexP) whose pH-dependent delivery was observed. The drug loaded Au@MIL nanocarrier shows high anti-inflammatory activity due to its capacity to specifically hinder inflammatory cell growth, scavenge intracellular reactive oxygen species (ROS) and downregulate pro-inflammatory cytokine secretion. In addition, this formulation has the capacity to inhibit the Toll-like receptor (TLR) signaling cascade namely the nuclear factor kappa B (NF-κB) and the interferon regulatory factor (IRF) pathways. This not only provides a new avenue for the nanotherapy of inflammatory diseases but also enhances our fundamental knowledge of the role of nanoMOF based nanomedicine in the regulation of innate immune signaling.

A hybrid cellulose-based programmable nanoplatform for applications in precision radiation oncology is described. Here, sugar heads work as tumor targeting moieties and steer the precise delivery of radiosensitizers, i.e. gold nanoparticles (AuNPs) into triple negative breast cancer (TNBC) cells. This "Trojan horse" approach promotes a specific and massive accumulation of radiosensitizers in TNBC cells, thus avoiding the fast turnover of small-sized AuNPs and the need for high doses of AuNPs for treatment. Application of X-rays resulted in a significant increase of the therapeutic effect while delivering the same dose, showing the possibility to use roughly half dose of X-rays to obtain the same radiotoxicity effect. These data suggest that this hybrid nanoplatform acts as a promising tool for applications in enhancing cancer radiotherapy effects with lower doses of X-rays.

Background: Dental pathogens play a crucial role in oral health issues, including tooth decay, gum disease, and oral infections, and recent research suggests a link between these pathogens and oral cancer initiation and progression. Innovative therapeutic approaches are needed due to antibiotic resistance concerns and treatment limitations., Methods: We synthesized and analyzed piperine-coated zinc oxide nanoparticles (ZnO-PIP NPs) using UV spectroscopy, SEM, XRD, FTIR, and EDAX. Antioxidant and antimicrobial effectiveness were evaluated through DPPH, ABTS, and MIC assays, while the anticancer properties were assessed on KB oral squamous carcinoma cells., Results: ZnO-PIP NPs exhibited significant antioxidant activity and a MIC of 50 µg/mL against dental pathogens, indicating strong antimicrobial properties. Interaction analysis revealed high binding affinity with dental pathogens. ZnO-PIP NPs showed dose-dependent anticancer activity on KB cells, upregulating apoptotic genes BCL2, BAX, and P53., Conclusions: This approach offers a multifaceted solution to combatting both oral infections and cancer, showcasing their potential for significant advancement in oral healthcare. It is essential to acknowledge potential limitations and challenges associated with the use of ZnO NPs in clinical applications. These may include concerns regarding nanoparticle toxicity, biocompatibility, and long-term safety. Further research and rigorous testing are warranted to address these issues and ensure the safe and effective translation of ZnO-PIP NPs into clinical practice., (© 2024. The Author(s).)

Photothermal therapy (PTT) is a promising clinical antitumor strategy. However, local hyperthermia inevitably induces heat damage to adjacent normal tissues, while alternative mild-temperature therapy (MPTT, T < 45 °C) is also inefficient due to the overexpressed hyperthermia-induced heat shock proteins (HSPs) by cancer cells. Therefore, developing PTT strategies with minimizing damage to healthy tissues with improved cellular temperature sensitivity is extremely valuable for clinical application. Herein, we proposed the strategy of disrupting the intracellular redox environment via destroying the ROS-defending systems to promote MPTT. The gold(III) porphyrin-Fe 3+ -tannic acid nanocomplexes (AuTPP@TA-Fe NPs) were achieved via interfacial cohesion and supramolecular assembly of bioadhesive species, which could trigger the Fenton reaction to produce ·OH radicals and downregulation of reductive TrxR enzyme and mitochondrial chaperone protein Hsp60. The aggravation of oxides and the inactivation of Hsp60 provide favorable pathways for impeding the heat shock-induced self-repair mechanism of cancer cells, which strengthens AuTPP@TA-Fe NPs mediated MPTT.