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Multifunctional nanoparticles (NPs) have gained considerable attention for cancer imaging and treatment. Herein, we develop novel multifunctional nanoprobes called SiO2@Au@Au porous shells (SiO2@Au@AuPS). SiO2@Au is fabricated by introducing 4 nm Au NPs to the thiol-modified SiO2 surface, after which alloy shells with different Ag/Au ratios are added. Shell modification is then implemented to obtain a porous structure via Ag etching using a dealloying reaction. Among the NPs, SiO2@Au@AuPS with an Au/Ag ratio of 1.5 (SiO2@Au@AuPS1.5) has a well-structured porous Au shell, with a number of nanogaps confirmed by the strongest Raman signal. Furthermore, SiO2@Au@AuPS decorated with PEG, 4-MBA, and anti-CD44 antibodies shows photothermal conversion effects under 980 nm, with a maximum drug loading capacity of 75.7 μg mg–1 for doxorubicin (DOX) and a releasing efficiency reaching 53.9% in a pH 6.0 buffer solution within 4 h. In vitro treatment of MDA-MB-231 breast cancer cells with SiO2@Au@AuPS1.5@PEG/4-MBA/anti-CD44/DOX decreases the cell viability to 20.3% under near-infrared laser irradiation with successful NP delivery and DOX release. Additionally, in vivo photothermal therapy/chemotherapy with tail-vein-injected SiO2@Au@AuPS1.5@PEG/4-MBA/anti-CD44/DOX is effective for cancer cell treatment. Our developed porous nanostructure presents possibilities for synergetic methods of effective photothermal treatment and drug delivery. [ABSTRACT FROM AUTHOR]

Nanotheranostics, combining photothermal therapy (PTT) and photodynamic therapy (PDT), can transform precision cancer treatment by integrating diagnosis and therapy into a single platform. This review highlights recent advances in nanomaterials, drug delivery systems, and stimuli-responsive mechanisms for effective PTT and PDT. Multifunctional nanoparticles enable targeted delivery, multimodal imaging, and controlled drug release, overcoming the challenges posed by tumor microenvironments. Emerging approaches such as hybrid therapies and immune activation further enhance therapeutic efficacy. This paper discusses the limitations of nanotheranostics, including synthesis complexity and limited tissue penetration, and explores future directions toward biocompatible, scalable, and clinically translatable solutions.

For more than two decades, nanoparticles have attracted a great deal of attention from researchers and developers. When properly designed, vectorized nanoparticles represent high-value-added tools with potentially invaluable properties in a number of areas, including biology, biotechnology, and medicine owing to their exceptional physico-chemical properties, especially resulting from their high surface area, high loading capacity, and nanoscale size. Smart design and building of nanoparticles through appropriate surface chemistry and functionalization provide a material that possesses multifunctional capabilities, able to specifically interact with a selected target, release a compound in a controlled and sustained way, and overcome, if desired, biological barriers such as the blood–brain barrier or lung barriers of interest. Unique constructions have thus opened up original and innovative possibilities in biotechnological and biomedical fields such as imaging, biosensors, rapid diagnostics, drug delivery, medical implants, and tissue engineering. This article briefly describes the main types of nanoparticles that have been developed and their advantages and disadvantages depending on the intended application, and highlights some remarkable results achieved recently in the biomedical field. Certain dangers or fears regarding their use in human and animal therapy or for users have been mentioned. Finally, conclusions and future perspectives are provided.

The development of effective therapies for neurological disorders is a growing area of research due to the increasing prevalence of these conditions. Some neurological disorders that are prevalent and remain difficult to treat are glioma, neurodegenerative disease, ischemic stroke, and traumatic brain injury. Subsequently, the therapeutic efficacy of small molecules, proteins, and oligonucleotides remains a challenge due to the presence of the blood–brain barrier (BBB), a highly selective semipermeable membrane. To this end, multifunctional nanomaterials have emerged as promising vehicles for targeted drug delivery to the brain, due to their ability to transport therapeutics across the BBB selectively. The design of advanced nanomaterial‐based drug delivery systems capable of overcoming the BBB is influenced by many factors, such as fabrication technique and surface modification. This review explores the diverse range of nanomaterials, including polymer, lipid, gold, magnetic, and carbon‐based nanostructures, capable of effectively passing the BBB. These materials cross the BBB via a variety of established transport mechanisms for targeted delivery of therapeutics to the brain. Moreover, the structure and function of the BBB are highlighted and the potential for nanotechnology to aid the treatment of neurological disorders based on their ability to undergo transcytosis into the brain is highlighted. [ABSTRACT FROM AUTHOR]

Nanotheranostics, combining photothermal therapy (PTT) and photodynamic therapy (PDT), can transform precision cancer treatment by integrating diagnosis and therapy into a single platform. This review highlights recent advances in nanomaterials, drug delivery systems, and stimuli-responsive mechanisms for effective PTT and PDT. Multifunctional nanoparticles enable targeted delivery, multimodal imaging, and controlled drug release, overcoming the challenges posed by tumor microenvironments. Emerging approaches such as hybrid therapies and immune activation further enhance therapeutic efficacy. This paper discusses the limitations of nanotheranostics, including synthesis complexity and limited tissue penetration, and explores future directions toward biocompatible, scalable, and clinically translatable solutions. [ABSTRACT FROM AUTHOR]

Minimally invasive medical treatments for peripheral nerve stimulation are critically needed to minimize surgical risks, enhance the precision of therapeutic interventions, and reduce patient recovery time. Magnetoelectric nanoparticles (MENPs), known for their unique ability to respond to both magnetic and electric fields, offer promising potential for precision medicine due to their dual tunable functionality. In this study a multi-physics modeling of the MENPs was performed, assessing their capability to be targeted through external magnetic fields and become electrically activated. In particular, by integrating electromagnetic, fluid dynamics, and biological models, the efficacy of MENPs as wireless nano-tools to trigger electrical stimulation in the peripheral Nervous system present within the dermal microenvironment was assessed. The simulations replicate the blood venous capillary network, accounting for the complex interactions between MENPs, blood flow, and vessel walls. Results demonstrate the precise steering of MENPs (>95%) toward target sites under a low-intensity external magnetic field (78 mT) even with a low susceptibility value (0.45). Furthermore, the extravasation and electrical activation of MENPs within the dermal tissue are analyzed, revealing the generation of high-induced electric fields in the surrounding area when MENPs are subjected to external magnetic fields. Overall, these findings predict that MENPs can be targeted in a tissue site when intravenously administrated, dragged through the microvessels of the venous system, and activated by generating high electric fields for the stimulation of the peripheral nervous system.

Abstract Background The main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects to shorten disease duration. Conventional root canal irrigants are limited in their efficacy and are associated with several side effects. This study introduces a synergistic therapy based on nitric oxide (NO) and antimicrobial photodynamic therapy (aPDT) for the treatment of apical periodontitis. Results This research developed a multifunctional nanoparticle, CGP, utilizing guanidinylated poly (ethylene glycol)-poly (ε-Caprolactone) polymer as a carrier, internally loaded with the photosensitizer chlorin e6. During root canal irrigation, the guanidino groups on the surface of CGP enabled effective biofilm penetration. These groups undergo oxidation by hydrogen peroxide in the aPDT process, triggering the release of NO without hindering the production of singlet oxygen. The generated NO significantly enhanced the antimicrobial capability and biofilm eradication efficacy of aPDT. Furthermore, CGP not only outperforms conventional aPDT in eradicating biofilms but also effectively promotes the repair of alveolar bone defects post-eradication. Importantly, our findings reveal that CGP exhibits significantly higher biosafety compared to sodium hypochlorite, alongside superior therapeutic efficacy in a rat model of apical periodontitis. Conclusions This study demonstrates that CGP, an effective root irrigation system based on aPDT and NO, has a promising application in root canal therapy.

Background: The main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects to shorten disease duration. Conventional root canal irrigants are limited in their efficacy and are associated with several side effects. This study introduces a synergistic therapy based on nitric oxide (NO) and antimicrobial photodynamic therapy (aPDT) for the treatment of apical periodontitis. Results: This research developed a multifunctional nanoparticle, CGP, utilizing guanidinylated poly (ethylene glycol)-poly (ε-Caprolactone) polymer as a carrier, internally loaded with the photosensitizer chlorin e6. During root canal irrigation, the guanidino groups on the surface of CGP enabled effective biofilm penetration. These groups undergo oxidation by hydrogen peroxide in the aPDT process, triggering the release of NO without hindering the production of singlet oxygen. The generated NO significantly enhanced the antimicrobial capability and biofilm eradication efficacy of aPDT. Furthermore, CGP not only outperforms conventional aPDT in eradicating biofilms but also effectively promotes the repair of alveolar bone defects post-eradication. Importantly, our findings reveal that CGP exhibits significantly higher biosafety compared to sodium hypochlorite, alongside superior therapeutic efficacy in a rat model of apical periodontitis. Conclusions: This study demonstrates that CGP, an effective root irrigation system based on aPDT and NO, has a promising application in root canal therapy. [ABSTRACT FROM AUTHOR]

How to develop antitumor nanodrugs with low toxicity and a good curative effect is an urgent problem in the current biomedicine field. In this work, different proposed composites were simulated by the finite difference time domain (FDTD) and COMSOL, including the material element, refractive index, particle size, and shape. Also, different machine learning algorithms are utilized to predict the absorbance at the near-infrared laser of 980 nm of different materials. Through train, validation, and test, the prediction of the as-synthesized Pt–Mn has high absorbance. Then, inorganic Pt–Mn was coated with PEI in order to improve their biocompatibility. Pt–Mn nanoparticles can generate ROS under the single 980 nm laser irradiation as a photodynamic therapy (PDT) agent and as a photothermal therapy (PTT) agent to heat the cells with a photothermal conversion efficiency of 23.6%. In addition, the electrochemical and in vitro chemodynamic therapy (CDT) experiments prove that Pt–Mn nanozymes could mimic the activity of peroxidase and enhance the Fenton reaction, thereby catalyzing excess H2O2 to produce hydroxyl free radicals and illustrating the potential to induce tumor cell apoptosis as the CDT agent in a weakly acidic tumor environment to complete high-efficiency chemokinetic therapy. Finally, Pt–Mn–PEI nanoparticles were used for PDT/PTT/CDT and the immune checkpoint inhibitor of anti-PD-L1 is injected in order to obtain the assistant immunotherapy, providing a potential choice to anticancer through effective synergistic cancer therapies. [ABSTRACT FROM AUTHOR]

The tumor microenvironment is a barrier to breast cancer therapy. Cancer-associated fibroblast cells (CAFs) can support tumor proliferation, metastasis, and drug resistance by secreting various cytokines and growth factors. Abnormal angiogenesis provides sufficient nutrients for tumor proliferation. Considering that CAFs express the sigma receptor (which recognizes anisamide, AA), we developed a CAFs and breast cancer cells dual-targeting nano drug delivery system to transport the LightOn gene express system, a spatiotemporal controlled gene expression consisting of a light-sensitive transcription factor and a specific minimal promoter. We adopted RGD (Arg-Gly-Asp) to selectively bind to the αvβ3 integrin on activated vascular endothelial cells and tumor cells. After the LightOn system has reached the tumor site, LightOn gene express system can spatiotemporal controllably express toxic Pseudomonas exotoxin An under blue light irradiation. The LightOn gene express system, combined with multifunctional nanoparticles, achieved high targeting delivery efficiency both in vitro and in vivo. It also displayed strong tumor and CAFs inhibition, anti-angiogenesis ability and anti-metastasis ability, with good safety. Moreover, it improved survival rate, survival time, and lung metastasis rate in a mouse breast cancer model. This study proves the efficacy of combining the LightOn system with targeted multifunctional nanoparticles in tumor and anti-metastatic therapy and provides new insights into tumor microenvironment regulation. [Display omitted] • pPEA@mNP is a multi-functional gene delivery system, with high targetability and sensitive release profile • pPEA@mNP can spatiotemporally inhibits tumor cells, cancer associated fibroblasts and tumor angiogenesis • pPEA@mNP can eliminate breast cancer and regulate tumor microenvironment, providing a novel anti-metastatic therapy strategy [ABSTRACT FROM AUTHOR]

Multifunctional nanoparticles are of significant importance for synergistic multimodal antitumor activity. Herein, zinc oxide (ZnO) was used as pH-sensitive nanoparticles for loading the chemotherapy agent doxorubicin (DOX) and the photosensitizer agent indocyanine green (ICG), and biocompatible low-molecular-weight heparin (LMHP) was used as the gatekeepers for synergistic photothermal therapy/photodynamic therapy/chemotherapy/immunotherapy. ZnO was decomposed into cytotoxic Zn2+ ions, leading to a tumor-specific release of ICG and DOX. ZnO simultaneously produced oxygen (O2) and reactive oxygen species (ROS) for photodynamic therapy (PDT). The released ICG under laser irradiation produced ROS for PDT and raised the tumor temperature for photothermal therapy (PTT). The released DOX directly caused tumor cell death for chemotherapy. Both DOX and ICG also induced immunogenic cell death (ICD) for immunotherapy. The in vivo and in vitro results presented a superior inhibition of tumor progression, metastasis and recurrence. Therefore, this study could provide an efficient approach for designing multifunctional nanoparticles for synergistic multimodal antitumor therapy. [ABSTRACT FROM AUTHOR]

Multifunctional particles with combined magnetic and optical properties are promising materials for applications such as sensing and detection of analytes, and contrast agents for imaging techniques such as MRI, and photocatalysis. While the magnetic property allows for non-contact manipulation of the nanoparticles, optical properties can be harnessed for such sensing applications. We present the synthesis and large-scale assembly of inter-layered magnetic-plasmonic nanoparticles with graphene oxide (GO) spacer (Fe3O4@GO@Ag). The multifunctional composite particles were prepared using simple chemical methods and had an average size of 225 nm. The prepared samples were characterized using different techniques including powder XRD, FT-IR, Raman scattering, SEM, and TEM imaging. By using an external magnetic field, it is possible to form an assembly of these multifunctional particles on a large scale. Due to the chain-like formation in the presence of a magnetic field, such assemblies are good substrates for surface-enhanced Raman scattering (SERS). Here, we demonstrate the application of these magnetically-assembled particles for the detection of very low concentrations of analyte molecules (4-mercaptopyridine) using SERS. These multifunctional composite particles are good candidates for potential applications involving chemical detection, photocatalytic reactions, optoelectronic devices, and photothermal effects. [ABSTRACT FROM AUTHOR]

In recent years, significant progress has been made in the surface functionalization of magnetic nanoparticles (MNPs), revolutionizing their utility in multimodal imaging, drug delivery, and catalysis. This progression, spanning over the last decade, has unfolded in discernible phases, each marked by distinct advancements and paradigm shifts. In the nascent stage, emphasis was placed on foundational techniques, such as ligand exchange and organic coatings, establishing the groundwork for subsequent innovations. This review navigates through the cutting-edge developments in tailoring MNP surfaces, illuminating their pivotal role in advancing these diverse applications. The exploration encompasses an array of innovative strategies such as organic coatings, inorganic encapsulation, ligand engineering, self-assembly, and bioconjugation, elucidating how each approach impacts or augments MNP performance. Notably, surface-functionalized MNPs exhibit increased efficacy in multimodal imaging, demonstrating improved MRI contrast and targeted imaging. The current review underscores the transformative impact of surface modifications on drug delivery systems, enabling controlled release, targeted therapy, and enhanced biocompatibility. With a comprehensive analysis of characterization techniques and future prospects, this review surveys the dynamic landscape of MNP surface functionalization over the past three years (2021–2023). By dissecting the underlying principles and applications, the review provides not only a retrospective analysis but also a forward-looking perspective on the potential of surface-engineered MNPs in shaping the future of science, technology, and medicine. [ABSTRACT FROM AUTHOR]

Polyelectrolyte microcapsules can be produced either by the layer-by-layer assembly technique or the formation of polyelectrolyte complexes at the liquid-liquid interface. Here, we describe the design and construction of DNA microcapsules using the cooperative assembly of DNA and amine-functionalized polyhedral oligomeric silsesquioxane (POSS-NH2) at the oil-water interface. "Janus-like" DNA surfactants (DNASs) assemble in situ at the interface, forming an elastic film. By controlling the jamming and unjamming behavior of DNASs, the interfacial assemblies can assume three different physical states: solid-like, elastomer-like, and liquid-like, similar to that seen with thermoplastics upon heating, that change from a glassy to a rubbery state, and then to a viscous liquid. By the interfacial jamming of DNASs, the liquid structures can be locked-in and reconfigured, showing promising potentials for drug delivery, biphasic reactors, and programmable liquid constructs.

Abstract Background The application of combination therapy for cancer treatment is limited due to poor tumor-specific drug delivery and the abscopal effect. Methods Here, PD-L1- and CD44-responsive multifunctional nanoparticles were developed using a polymer complex of polyethyleneimine and oleic acid (PEI-OA) and loaded with two chemotherapeutic drugs (paclitaxel and chloroquine), an antigen (ovalbumin), an immunopotentiator (CpG), and an immune checkpoint inhibitor (anti-PD-L1 antibody). Results PEI-OA greatly improved the drug loading capacity and encapsulation efficiency of the nanoplatform, while the anti-PD-L1 antibody significantly increased its cellular uptake compared to other treatment formulations. Pharmacodynamic experiments confirmed that the anti-PD-L1 antibody can strongly inhibit primary breast cancer and increase levels of CD4+ and CD8+ T cell at the tumor site. In addition, chloroquine reversed the “immune-cold” environment and improved the anti-tumor effect of both chemotherapeutics and immune checkpoint inhibitors, while it induced strong immune memory and prevented lung metastasis. Conclusions Our strategy serves as a promising approach to the rational design of nanodelivery systems for simultaneous active targeting, autophagy inhibition, and chemotherapy that can be combined with immune-checkpoint inhibitors for enhanced breast cancer treatment.

Abstract Background Disruption of the postsynaptic density protein-95 (PSD95)—neuronal nitric oxide synthase (nNOS) coupling is an effective way to treat ischemic stroke, however, it still faces some challenges, especially lack of satisfactory PSD95-nNOS uncouplers and the efficient high throughput screening model to discover them. Results Herein, the multifunctional metal–organic framework (MMOF) nanoparticles as a new screening system were innovatively fabricated via layer-by-layer self-assembly in which His-tagged nNOS was selectively immobilized on the surface of magnetic MOF, and then PSD95 with green fluorescent protein (GFP-PSD95) was specifically bound on it. It was found that MMOF nanoparticles not only exhibited the superior performances including the high loading efficiency, reusability, and anti-interference ability, but also possessed the good fluorescent sensitivity to detect the coupled GFP-PSD95. After MMOF nanoparticles interacted with the uncouplers, they would be rapidly separated from uncoupled GFP-PSD95 by magnet, and the fluorescent intensities could be determined to assay the uncoupling efficiency at high throughput level. Conclusions In conclusion, MMOF nanoparticles were successfully fabricated and applied to screen the natural actives as potential PSD95-nNOS uncouplers. Taken together, our newly developed method provided a new material as a platform for efficiently discovering PSD95-nNOS uncouplers for stoke treatment. Graphical Abstract

Curcumin (Cur) is a natural polyphenol that is one of the most valuable natural products. However, its use as a functional food is limited by low water solubility, chemical instability and poor bioavailability. In this study, a supramolecular co-assembly strategy was used to construct an oleanolic acid-curcumin (OLA-Cur) co-assembly composite nano-slow-release treatment system. As a co-assembled compound, OLA is a widely present pentacyclic triterpenoid compound with multiple biological activities in the plant kingdom, which is expected to jointly alleviate the damaging effects of papain-induced mouse osteoarthritis model. The OLA-Cur NPs shows the solid core-shell structure, which can effectively improve the water solubility of Cur and OLA, and has good stability and sustained release characteristics. The analysis results show that the two compounds are mainly assembled through hydrogen bonding interactions, hydrophobic interactions, and π - π stacking interactions. The OLA-Cur NPs can inhibit the release of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β induced by LPS in RAW264.7 mouse macrophages, promote the secretion of anti-inflammatory cytokine IL-10, and improve the oxidative stress index of hydrogen peroxide induced human rheumatoid arthritis synovial fibroblasts. In addition, it has a certain improvement effect on cartilage and subchondral bone damage in mouse osteoarthritis models. These findings suggest that constructing co-assembled composite nanoparticles based on pure natural compounds may break through the limitations of a variety of important nutritional ingredients in functional foods. [Display omitted] • OLA-Cur NPs solve the problems of low water solubility, chemical instability, and poor bioavailability of curcumin. • OLA-Cur NPs improve the water solubility of Cur and OLA and maintaining good stability and sustained-release properties. • OLA and Cur form stable composite structures through supramolecular interactions, enhancing their biological activity. • OLA-Cur has both anti-inflammatory and antioxidant effects, demonstrating good therapeutic potential for osteoarthritis mice. [ABSTRACT FROM AUTHOR]

Multifunctional nanoparticles are of significant importance for synergistic multimodal antitumor activity. Herein, zinc oxide (ZnO) was used as pH-sensitive nanoparticles for loading the chemotherapy agent doxorubicin (DOX) and the photosensitizer agent indocyanine green (ICG), and biocompatible low-molecular-weight heparin (LMHP) was used as the gatekeepers for synergistic photothermal therapy/photodynamic therapy/chemotherapy/immunotherapy. ZnO was decomposed into cytotoxic Zn2+ ions, leading to a tumor-specific release of ICG and DOX. ZnO simultaneously produced oxygen (O2) and reactive oxygen species (ROS) for photodynamic therapy (PDT). The released ICG under laser irradiation produced ROS for PDT and raised the tumor temperature for photothermal therapy (PTT). The released DOX directly caused tumor cell death for chemotherapy. Both DOX and ICG also induced immunogenic cell death (ICD) for immunotherapy. The in vivo and in vitro results presented a superior inhibition of tumor progression, metastasis and recurrence. Therefore, this study could provide an efficient approach for designing multifunctional nanoparticles for synergistic multimodal antitumor therapy.

Magnetic Resonance Imaging (MRI) T1 contrast agents based on Fe(III) as an alternative to Gd‐based compounds have been under intense scrutiny in the last 6–8 years and a number of nanostructures have been designed and proposed for in vivo diagnostic and theranostic applications. Excluding the large family of superparamagnetic iron oxides widely used as T2‐MR imaging agents that will not be covered by this review, a considerable number and type of nanoparticles (NPs) have been employed, ranging from amphiphilic polymer‐based NPs, NPs containing polyphenolic binding units such as melanin‐like or polycatechols, mixed metals such as Fe/Gd or Fe/Au NPs and perfluorocarbon nanoemulsions. Iron(III) exhibits several favorable magnetic properties, high biocompatibility and improved toxicity profile that place it as the paramagnetic ion of choice for the next generation of nanosized MRI and theranostic contrast agents. An analysis of the examples reported in the last decade will show the opportunities for relaxivity and MR‐contrast enhancement optimization that could bring Fe(III)‐doped NPs to really compete with Gd(III)‐based nanosystems. This article is categorized under:Diagnostic Tools > In Vivo Nanodiagnostics and ImagingDiagnostic Tools > Diagnostic NanodevicesTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease [ABSTRACT FROM AUTHOR]

Unlike any other nanoparticles known to date, magnetoelectric nanoparticles (MENPs) can generate relatively strong electric fields locally via the application of magnetic fields and, vice versa, have their magnetization change in response to an electric field from the microenvironment. Hence, MENPs can serve as a wireless two‐way interface between man‐made devices and physiological systems at the molecular level. With the recent development of room‐temperature biocompatible MENPs, a number of novel potential medical applications have emerged. These applications include wireless brain stimulation and mapping/recording of neural activity in real‐time, targeted delivery across the blood–brain barrier (BBB), tissue regeneration, high‐specificity cancer cures, molecular‐level rapid diagnostics, and others. Several independent in vivo studies, using mice and nonhuman primates models, demonstrated the capability to deliver MENPs in the brain across the BBB via intravenous injection or, alternatively, bypassing the BBB via intranasal inhalation of the nanoparticles. Wireless deep brain stimulation with MENPs was demonstrated both in vitro and in vivo in different rodents models by several independent groups. High‐specificity cancer treatment methods as well as tissue regeneration approaches with MENPs were proposed and demonstrated in in vitro models. A number of in vitro and in vivo studies were dedicated to understand the underlying mechanisms of MENPs‐based high‐specificity targeted drug delivery via application of d.c. and a.c. magnetic fields. This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in BiologyTherapeutic Approaches and Drug Discovery > Nanomedicine for Neurological DiseaseTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseTherapeutic Approaches and Drug Discovery > Emerging Technologies [ABSTRACT FROM AUTHOR]

Cancer is a complex disease associated with a combination of abnormal physiological process and exhibiting dysfunctions in multiple systems. To provide effective treatment and diagnosis for cancer, current treatment strategies simultaneously focus on various tumor targets. Based on the rapid development of nanotechnology, nanocarriers have been shown to exhibit excellent potential for cancer therapy. Compared with nanoparticles with single functions, multifunctional nanoparticles are believed to be more aggressive and potent in the context of tumor targeting. However, the development of multifunctional nanoparticles is not simply an upgraded version of the original function, but involves a sophisticated system with a proper backbone, optimized modification sites, simple preparation method, and efficient function integration. Despite this, many well‐designed multifunctional nanoparticles with promising therapeutic potential have emerged recently. Here, to give a detailed understanding and analyzation of the currently developed multifunctional nanoparticles, their platform structures with organic or inorganic backbones were systemically generalized. We emphasized on the functionalization and modification strategies, which provide additional functions to the nanoparticle. We also discussed the application combination strategies that were involved in the development of nanoformulations with functional crosstalk. This review thus provides an overview of the construction strategies and application advances of multifunctional nanoparticles. [ABSTRACT FROM AUTHOR]

Cancer cells possess distinct bioelectrical properties, yet therapies leveraging these characteristics remain underexplored. Herein, we introduce an innovative nanobioelectronic system combining a piezoelectric barium titanate nanoparticle core with a conducting poly(3,4-ethylenedioxythiophene) shell (BTO@PEDOT NPs), designed to modulate cancer cell bioelectricity through noninvasive, wireless stimulation. Our hypothesis is that acting as nanoantennas, BTO@PEDOT NPs convert mechanical inputs provided by ultrasound (US) into electrical signals, capable of interfering with the bioelectronic circuitry of two human breast cancer cell lines, MCF-7 and MDA-MB-231. Upon US stimulation, the viability of MCF-7 and MDA-MB-231 cells treated with 200 μg mL -1 BTO@PEDOT NPs and US reduced significantly to 31% and 24%, respectively, while healthy human mammary fibroblasts (HMF) were unaffected by the treatment. Subsequent assays shed light on how this approach could interact with cell's bioelectrical mechanisms, namely, by increasing intracellular reactive oxygen species (ROS) and calcium concentrations. Furthermore, this system was able to polarize cancer cell membranes, halting their cell cycle and potentially harnessing their tumorigenic characteristics. These findings underscore the crucial role of bioelectricity in cancer progression and highlight the potential of nanobioelectronic systems as an emerging and promising strategy for cancer intervention.

With polymer nanoparticles now playing an influential role in biological applications, the synthesis of nanoparticles with precise control over size, shape, and chemical functionality, along with a responsive ability to environmental changes, remains a significant challenge. To address this challenge, innovative polymerization methods must be developed that can incorporate diverse functional groups and stimuli-responsive moieties into polymer nanostructures, which can then be tailored for specific biological applications. By combining the advantages of emulsion polymerization in an environmentally friendly reaction medium, high polymerization rates due to the compartmentalization effect, chemical functionality, and scalability, with the precise control over polymer chain growth achieved through reversible-deactivation radical polymerization, our group developed the temperature-directed morphology transformation (TDMT) method to produce polymer nanoparticles. This method utilized temperature or pH responsive nanoreactors for controlled particle growth and with the added advantages of controlled surface chemical functionality and the ability to produce well-defined asymmetric structures (e.g., tadpoles and kettlebells). This review summarizes the fundamental thermodynamic and kinetic principles that govern particle formation and control using the TDMT method, allowing precision-engineered polymer nanoparticles, offering a versatile and an efficient means to produce 3D nanostructures directly in water with diverse morphologies, high purity, high solids content, and controlled surface and internal functionality. With such control over the nanoparticle features, the TDMT-generated nanostructures could be designed for a wide variety of biological applications, including antiviral coatings effective against SARS-CoV-2 and other pathogens, reversible scaffolds for stem cell expansion and release, and vaccine and drug delivery systems.

Urinalysis is one of the predominant tools for clinical testing owing to the abundant composition, sufficient volume, and non-invasive acquisition of urine. As a critical component of routine urinalysis, urine protein testing measures the levels and types of proteins, enabling the early diagnosis of diseases. Traditional methods require three separate steps including strip testing, protein/creatinine ratio measurement, and electrophoresis respectively to achieve qualitative, quantitative, and classification analyses of proteins in urine with long time and cumbersome operations. Herein, this work demonstrates a "three-in-one" protocol to analyze the urine composition by combining multifunctional nanoparticles with machine learning. This work constructs a sensor array to analyze proteinuria by employing nanoparticles with unique optical properties, outstanding catalytic activity, diverse composition, and tunable structure as probes. Different proteins interacted with nanoprobes differently and are classified by this sensor array based on their physicochemical heterogeneities. With the aid of machine learning, the urine composition is precisely detected for the diagnosis of bladder cancer. This protocol enables quantification and classification of 5 proteinuria in 10 min without any tedious pretreatment, showing proimise for the comprehensive analysis of body fluid for early disease diagnosis., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The systemic toxicity and low efficacy of traditional chemotherapy for hepatocellular carcinoma (HCC) result in poor clinical outcomes. This study was designed to achieve targeted delivery of apoptin plasmid (AP) to liver tumors and killing of cancer cells using multifunctional nanoparticles (MFNPs) having sustained-release properties. The MFNPs featuring a distinct core-shell structure were prepared using poly(lactic-glycolic acid)-ε-polylysine copolymer and loaded with AP by adsorption. Specific targeting of liver tumor cells was achieved by biotinylation of the nanoparticles (NPs), while an improvement in lysosomal escape and nuclear localization enhanced the tumor cell killing capability of AP. Blank MFNPs exhibited good biocompatibility while AP-loaded NPs were found to exert strong inhibitory effects on both tumor cells in vitro and solid tumors in vivo. Taken together, these findings demonstrate a promising route for the development of tumor-targeted NPs which may lead to improved therapeutic strategies for treating HCC.

Abstract Cancer is a complex disease associated with a combination of abnormal physiological process and exhibiting dysfunctions in multiple systems. To provide effective treatment and diagnosis for cancer, current treatment strategies simultaneously focus on various tumor targets. Based on the rapid development of nanotechnology, nanocarriers have been shown to exhibit excellent potential for cancer therapy. Compared with nanoparticles with single functions, multifunctional nanoparticles are believed to be more aggressive and potent in the context of tumor targeting. However, the development of multifunctional nanoparticles is not simply an upgraded version of the original function, but involves a sophisticated system with a proper backbone, optimized modification sites, simple preparation method, and efficient function integration. Despite this, many well‐designed multifunctional nanoparticles with promising therapeutic potential have emerged recently. Here, to give a detailed understanding and analyzation of the currently developed multifunctional nanoparticles, their platform structures with organic or inorganic backbones were systemically generalized. We emphasized on the functionalization and modification strategies, which provide additional functions to the nanoparticle. We also discussed the application combination strategies that were involved in the development of nanoformulations with functional crosstalk. This review thus provides an overview of the construction strategies and application advances of multifunctional nanoparticles.

Background: The application of combination therapy for cancer treatment is limited due to poor tumor-specific drug delivery and the abscopal effect.Methods: Here, PD-L1- and CD44-responsive multifunctional nanoparticles were developed using a polymer complex of polyethyleneimine and oleic acid (PEI-OA) and loaded with two chemotherapeutic drugs (paclitaxel and chloroquine), an antigen (ovalbumin), an immunopotentiator (CpG), and an immune checkpoint inhibitor (anti-PD-L1 antibody).Results: PEI-OA greatly improved the drug loading capacity and encapsulation efficiency of the nanoplatform, while the anti-PD-L1 antibody significantly increased its cellular uptake compared to other treatment formulations. Pharmacodynamic experiments confirmed that the anti-PD-L1 antibody can strongly inhibit primary breast cancer and increase levels of CD4+ and CD8+ T cell at the tumor site. In addition, chloroquine reversed the "immune-cold" environment and improved the anti-tumor effect of both chemotherapeutics and immune checkpoint inhibitors, while it induced strong immune memory and prevented lung metastasis.Conclusions: Our strategy serves as a promising approach to the rational design of nanodelivery systems for simultaneous active targeting, autophagy inhibition, and chemotherapy that can be combined with immune-checkpoint inhibitors for enhanced breast cancer treatment. [ABSTRACT FROM AUTHOR]

Multifunctional magnetic nanoparticles (MNPs) exhibit unique properties, such as remote motion controllability, degradability, and diagnostic imaging, which are typically not shown in nonmagnetic nanomaterials. MNPs remotely controllable via magnetic fields offer advantages of high tissue penetrability and biocompatibility. In this review, recent advances of multifunctional MNPs exhibiting unique characteristic for therapeutic applications are summarized, which utilize the “dynamic” motion, iron ion degradation, or imaging‐guided targeting of the MNPs under diverse magnetic field modes. The magnetic field‐controlled MNP motion enables spatiotemporal and reversible in situ cell regulation and mechanosensitive molecule modulation or thermal energy generation. Furthermore, the iron‐based MNPs can produce degraded ions and reactive oxygen species to enable targeted ferroptosis therapy with medical imaging‐guided approaches. The state‐of‐the‐art imaging‐guided “dynamic” therapy using the MNPs that can provide in situ feedback at each therapeutic stage is highlighted. Potential hurdles in translating the magnetic dynamic imaging and therapy toward clinical practices are also discussed. The imaging capability of the MNPs during “dynamic” magneto‐cell regulation enables noninvasive, safe, localized, and on‐demand regulation for the state‐of‐the‐art regenerative therapy, immunotherapy, and cancer treatment.

Background: Disruption of the postsynaptic density protein-95 (PSD95)—neuronal nitric oxide synthase (nNOS) coupling is an effective way to treat ischemic stroke, however, it still faces some challenges, especially lack of satisfactory PSD95-nNOS uncouplers and the efficient high throughput screening model to discover them. Results: Herein, the multifunctional metal–organic framework (MMOF) nanoparticles as a new screening system were innovatively fabricated via layer-by-layer self-assembly in which His-tagged nNOS was selectively immobilized on the surface of magnetic MOF, and then PSD95 with green fluorescent protein (GFP-PSD95) was specifically bound on it. It was found that MMOF nanoparticles not only exhibited the superior performances including the high loading efficiency, reusability, and anti-interference ability, but also possessed the good fluorescent sensitivity to detect the coupled GFP-PSD95. After MMOF nanoparticles interacted with the uncouplers, they would be rapidly separated from uncoupled GFP-PSD95 by magnet, and the fluorescent intensities could be determined to assay the uncoupling efficiency at high throughput level. Conclusions: In conclusion, MMOF nanoparticles were successfully fabricated and applied to screen the natural actives as potential PSD95-nNOS uncouplers. Taken together, our newly developed method provided a new material as a platform for efficiently discovering PSD95-nNOS uncouplers for stoke treatment. [ABSTRACT FROM AUTHOR]

Hongmei Liu,1,2 Minghao Yuan,1,2 Yushi Liu,1,2 Yiping Guo,3 Haijun Xiao,4 Li Guo,1,2 Fei Liu1,2 1School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 2State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu, 611137, People’s Republic of China; 3Quantitative and Systems Biology Program, University of California, Merced, CA, 95343, USA; 4Centre of Polymer Systems, Tomas Bata University in Zlin, Zlin, 76001, Czech RepublicCorrespondence: Li GuoChengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of ChinaTel +86 28-61800237Email guoli@cdutcm.edu.cnPurpose: Due to the shortcomings of nanocarriers, the development of carrier-free nanodelivery systems has attracted more and more attention in cancer treatment. However, there are few studies on carrier-free nanosystems that can simultaneously achieve monitoring functions. Here a multifunctional carrier-free nanosystem loaded with curcumin and irinotecan hydrochloride was established for the treatment and monitoring of gastric cancer.Methods: In this study, an irinotecan hydrochloride-curcumin nanosystem in the early stage (the system is named SICN) was prepared. Based on the fluorescence of curcumin, flow cytometry, laser confocal microscopy, and zebrafish fluorescence imaging were used to study the monitoring function of SICN in vivo and in vitro. In addition, HGC-27 human gastric cancer cells were used to study SICN cytotoxicity.Results: Flow cytometry and zebrafish fluorescence imaging monitoring results showed that the uptake of SICN was significantly higher than free curcumin, and the excretion rate was lower. SICN had higher accumulation and retention in cells and zebrafish. Laser confocal microscopy monitoring results showed that SICN was internalized into HGC-27 cells through multiple pathways, including macropinocytosis, caveolin, and clathrin-mediated and clathrin -independent endocytosis, and distributed intracellularly throughout the whole cytoplasm, including lysosomes and Golgi apparatus. In vitro cell experiments showed that SICN nanoparticles were more toxic than single components, and HGC-27 cells had more absorption and higher toxicity to nanoparticles under slightly acidic conditions.Conclusion: SICN is a promising carrier-free nanoparticle, and the combination of two single-component therapies can exert a synergistic antitumor effect. When exposed to a tumor acidic environment, SICN showed stronger cytotoxicity due to charge conversion. More importantly, the nanoparticles’ self-monitoring function has been developed, opening up new ideas for combined tumor therapy.Keywords: carrier-free, irinotecan hydrochloride, curcumin, multifunctional nanoparticles

The interest in the use of green-mediated synthesis of nanoparticles (NPs) is shown to have increased due to their biocompatibility and reduction of overall production costs. The current study aimed to evaluate a novel nanocomposite (NC) prepared by using a combination of zinc oxide, silver and chitosan with lemon extract as a cross-linking agent and assessed its antimicrobial effectiveness against Enterococcus faecalis (E. faecalis). The NPs and NC were prepared individually using a modification of previously established methods. Ananalys is of the physiochemical properties of the NC was conducted using ultraviolet-visible spectroscopy (UV-Vis) (Shimadzu Corporation, Kyoto, Japan). and transmission electron microscopy (TEM) imaging(HR-TEM; JEOL Ltd., Akishima-shi, Japan. The microbial reduction with this novel NC was evaluated by measuring the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using a tube assay analytic technique. A time-kill assay analysis was conducted to evaluate the kinetic potential against E. faecalis at different time intervals. The novel NC showed a homogenous nanoparticle size under TEM imaging and under UV-Vis established an absorption range of 350–420 nm making it similar to its individual counterparts. The MIC and MIB were measured at 62.5 ± 20 mg/L (p < 0.05) and 250 ± 72 mg/L (p < 0.05), respectively. A time-kill assay analysis for the NC showed 5 h was required to eradicate E. faecalis. Based on the achieved results, it was seen that the novel NC using a combination of silver, zinc oxide and chitosan showed improved antimicrobial action against E. faecalis compared with its individual components under laboratory conditions. A complete eradication of 108 log units of E. faecalis at 250 mg/L occurred after a total of 5 h. These preliminary results establish the use of lemon extract-mediated silver, zinc and chitosan-based NC had an antibacterial effectiveness against E. faecalis similar to the individual counterparts used for its production under laboratory conditions. [ABSTRACT FROM AUTHOR]

In the recent past, nanotechnological advancements in engineered nanomaterials have demonstrated diverse and versatile applications in different arenas, including bio-imaging, drug delivery, bio-sensing, detection and analysis of biological macromolecules, bio-catalysis, nanomedicine, and other biomedical applications. However, public interests and concerns in the context of human exposure to these nanomaterials and their consequential well-being may hamper the wider applicability of these nanomaterial-based platforms. Furthermore, human exposure to these nanosized and engineered particulate materials has also increased drastically in the last 2 decades due to enormous research and development and anthropocentric applications of nanoparticles. Their widespread use in nanomaterial-based industries, viz., nanomedicine, cosmetics, and consumer goods has also raised questions regarding the potential of nanotoxicity in general and reproductive nanotoxicology in particular. In this review, we have summarized diverse aspects of nanoparticle safety and their toxicological outcomes on reproduction and developmental systems. Various research databases, including PubMed and Google Scholar, were searched for the last 20 years up to the date of inception, and nano toxicological aspects of these materials on male and female reproductive systems have been described in detail. Furthermore, a discussion has also been dedicated to the placental interaction of these nanoparticles and how these can cross the blood–placental barrier and precipitate nanotoxicity in the developing offspring. Fetal abnormalities as a consequence of the administration of nanoparticles and pathophysiological deviations and aberrations in the developing fetus have also been touched upon. A section has also been dedicated to the regulatory requirements and guidelines for the testing of nanoparticles for their safety and toxicity in reproductive systems. It is anticipated that this review will incite a considerable interest in the research community functioning in the domains of pharmaceutical formulations and development in nanomedicine-based designing of therapeutic paradigms.

Background: Pancreatic cancer is a highly malignant tumor, which is still a major global health problem. Chemotherapy and radiotherapy are regularly used in adjuvant therapy for pancreatic cancer but their therapeutic efficacy is limited., Methods: In the present study, nanoparticle（MSN-AuNPs） was used as a drug carrier loaded with tirapazamine(TPZ) and hyaluronic acid (HA) to synthesize a multifunctional nanoplatform HA@TPZ-MSN-AuNPs (HTMA) for hypoxia activation and radiotherapy sensitization, which can be combined with radiotherapy therapy and synergistically enhance the therapeutic effect in pancreatic cancer. The anti-tumor performance of the nano platform was verified by in vivo and in vitro experiments., Result: First, the HA@TPZ-MSN-AuNPs (HTMA) was successfully synthesized. Drug release experiments showed that acidic environment and hyaluronidase promoted drug release in the nanoplatform. In vitro experiments, CCK-8, live-dead staining, clonal formation assay and flow cytometry confirmed the combined anti-tumor effect of hypoxia activation and radiotherapy sensitization with HTMA. In the drug uptake experiment, the nanoplatform showed the function of targeting and binding pancreatic cancer cells. In vivo, HTMA demonstrated good antitumor properties and good biocompatibility., Conclusions: The nanoplatform had a good targeting effect and synergistic anti-tumor effect. The combination of hypoxia activation and radiotherapy sensitization is a promising strategy for the treatment of pancreatic cancer., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Tuberculosis is a major global health problem for which improved therapeutics are needed to shorten the course of treatment and combat emergence of drug resistance. Mycobacterium tuberculosis, the etiologic agent of tuberculosis, is an intracellular pathogen of mononuclear phagocytes. As such, it is an ideal pathogen for nanotherapeutics because macrophages avidly ingest nanoparticles even without specific targeting molecules. Hence, a nanoparticle drug delivery system has the potential to target and deliver high concentrations of drug directly into M. tuberculosis-infected cells-greatly enhancing efficacy while avoiding off-target toxicities. Stimulus-responsive mesoporous silica nanoparticles of two different sizes, 100 and 50 nm, are developed as carriers for the major anti-tuberculosis drug isoniazid in a prodrug configuration. The drug is captured by the aldehyde-functionalized nanoparticle via hydrazone bond formation and coated with poly(ethylene imine)-poly(ethylene glycol) (PEI-PEG). The drug is released from the nanoparticles in response to acidic pH at levels that naturally occur within acidified endolysosomes. It is demonstrated that isoniazid-loaded PEI-PEG-coated nanoparticles are avidly ingested by M. tuberculosis-infected human macrophages and kill the intracellular bacteria in a dose-dependent manner. It is further demonstrated in a mouse model of pulmonary tuberculosis that the nanoparticles are well tolerated and much more efficacious than an equivalent amount of free drug.

On page 5066, J. I. Zink, M. A. Horwitz, and co-workers use confocal microscopy to demonstrate the avid uptake of RITC-labeled mesoporous silica nanoparticles loaded with the anti-tuberculosis drug isoniazid (shown here in red) by human macrophages (nuclei stained blue with DAPI) infected with GFP-expressing Mycobacterium tuberculosis (shown here in green).

Wan Xie,1,2 Shenyin Zhu,3 Biyong Yang,4 Chunyan Chen,1 Shuning Chen,1 Yujiao Liu,1 Xuyuan Nie,5 Lan Hao,2 Zhigang Wang,2 Jiangchuan Sun,1 Shufang Chang1 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 2Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 4Chongqing Institute for Food and Drug Control, Chongqing 401121, People’s Republic of China; 5School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, People’s Republic of ChinaCorrespondence: Shufang Chang; Jiangchuan SunDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjian Road, Yuzhong District, Chongqing 400010, People’s Republic of ChinaTel +86 023 6369 3279Fax +86 023 6510 4238Email shfch2018@hospital.cqmu.edu.cn; sunjiangchuan@126.comPurpose: Photodynamic therapy (PDT), sonodynamic therapy (SDT), and oxaliplatin (OXP) can induce immunogenic cell death (ICD) following damage-associated molecular patterns (DAMPs) exposure or release and can be united via the use of nanoplatforms to deliver drugs that can impart anti-tumor effects. The aim of this study was to develop phase-transition nanoparticles (OI_NPs) loaded with perfluoropentane (PFP), indocyanine green (ICG), and oxaliplatin (OXP), to augment anti-tumor efficacy and the immunological effects of chemotherapy, photodynamic therapy and sonodynamic therapy (PSDT).Methods: OI_NPs were fabricated by a double emulsion method and a range of physicochemical and dual-modal imaging features were characterized. Confocal microscopy and flow cytometry were used to determine the cellular uptake of OI_NPs by ID8 cells. The viability and apoptotic rate of ID8 cells were investigated using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry. Flow cytometry, Western blotting, and luminometric assays were then used to investigate the exposure or release of crucial DAMPs such as calreticulin (CRT), high mobility group box 1 (HMGB1), and adenosine-5ʹ-triphosphate (ATP). Tumor rechallenge experiments were then used to investigate whether treated ID8 cells underwent ICD. Finally, cytotoxic T lymphocyte (CTL) activity was determined by a lactate dehydrogenase (LDH) assay.Results: Spherical OI_NPs were able to carry OXP, ICG and PFP and were successfully internalized by ID8 cells. The application of OI_NPs significantly enhanced the phase shift ability of PFP and the optical characteristics of ICG, thus leading to a significant improvement in photoacoustic and ultrasonic imaging. When combined with near-infrared light and ultrasound, the application of OI_NPs led to improved anti-tumor effects on cancer cells, and significantly enhanced the expression of DAMPs, thus generating a long-term anti-tumor effect.Conclusion: The application of OI_NPs, loaded with appropriate cargo, may represent a novel strategy with which to increase anti-tumor effects, enhance immunological potency, and improve dual-mode imaging.Keywords: ovarian cancer, multifunctional nanoparticles, photo-sonodynamic therapy, immunogenic cell death, reactive oxygen species