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Low migratory dendritic cell (DC) levels pose a challenge in cancer immune surveillance, yet their impact on tumor immune status and immunotherapy responses remains unclear. We present clinical evidence linking reduced migratory DC levels to immune-cold tumor status, resulting in poor patient outcomes. To address this, we develop an autologous DC-based nanovaccination strategy using patient-derived organoid or cancer cell lysate-pulsed cationic nanoparticles (cNPs) to load immunogenic DC-derived microvesicles (cNP cancer cell @MV DC ). This approach transforms immune-cold tumors, increases migratory DCs, activates T cells and natural killer cells, reduces tumor growth, and enhances survival in orthotopic pancreatic and lung cancer models, surpassing conventional methods. In vivo imaging reveals superior cNP cancer cell @MV DC accumulation in tumors and lymph nodes, promoting immune cell infiltration. Mechanistically, cNPs enrich mitochondrial DNA, enhancing cGAS-STING-mediated DC activation and migration. Our strategy shifts cold tumors to a hot state, enhancing antitumor immunity for potential personalized cancer treatments., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

By 2050, the global population is projected to reach 9 billion, underscoring the imperative for innovative solutions to increase grain yield and enhance food security. Nanotechnology has emerged as a powerful tool, providing unique solutions to this challenge. Nanoparticles (NPs) can improve plant growth and nutrition under normal conditions through their high surface-to-volume ratio and unique physical and chemical properties. Moreover, they can be used to monitor crop health status and augment plant resilience against abiotic stresses (such as salinity, drought, heavy metals, and extreme temperatures) that endanger global agriculture. Application of NPs can enhance stress tolerance mechanisms in plants, minimizing potential yield losses and underscoring the potential of NPs to raise crop yield and quality. This review highlights the need for a comprehensive exploration of the environmental implications and safety of nanomaterials and provides valuable guidelines for researchers, policymakers, and agricultural practitioners. With thoughtful stewardship, nanotechnology holds immense promise in shaping environmentally sustainable agriculture amid escalating environmental challenges., (© 2024 Institute of Botany, Chinese Academy of Sciences.)

Precise diagnosis of complex and soft tumors is challenging, which limits appropriate treatment options to achieve desired therapeutic outcomes. However, multifunctional nano-sized contrast enhancement agents based on nanoparticles improve the diagnosis accuracy of various diseases such as cancer. Herein, a facile manganese-hafnium nanocomposites (Mn 3 O 4 -HfO 2 NCs) system was designed for bimodal magnetic resonance imaging (MRI)/computed tomography (CT) contrast enhancement with a complimentary function of photodynamic therapy. The solvothermal method was used to fabricate NCs, and the average size of Mn 3 O 4 NPs and Mn 3 O 4 -HfO 2 NCs was about 7 nm and 15 nm, respectively, as estimated by TEM. Dynamic light scattering results showed good dispersion and high negative (-33 eV) zeta potential, indicating excellent stability in an aqueous medium. Mn 3 O 4 -HfO 2 NCs revealed negligible toxic effects on the NCTC clone 929 (L929) and mouse colon cancer cell line (CT26), demonstrating promising biocompatibility. The synthesized Mn 3 O 4 -HfO 2 NCs exhibit significant enhancement in T 1 -weighted magnetic resonance imaging (MRI) and X-ray computed tomography (CT), indicating the appropriateness for dual-modal MRI/CT molecular imaging probes. Moreover, ultra-small Mn 3 O 4 -HfO 2 NCs show good relaxivities for MRI/CT. These nanoprobes Mn 3 O 4 -HfO 2 NCs further possessed outstanding reactive oxygen species (ROS) generation ability under minute ultraviolet light (6 mW·cm -2 ) to ablate the colon cancer cells in vitro. Therefore, the designed multifunctional Mn 3 O 4 -HfO 2 NCs were ideal candidates for cancer diagnosis and photodynamic therapy., 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.)

The concept of combining external medical stimuli with internal functional biomaterials to achieve cancer-oriented treatments is being emergingly developed. Optical and acoustical activations have shown particular promise as non-invasive regulation modalities in cancer treatment and intervention. It is always challenging to leverage the contributions of optical and acoustical stimuli and find appropriate biomaterials to optimally match them. Herein, a type of hybrid nanomicelle (ICG@PEP@HA) containing ICG as a photo/sonosensitizer, an amphiphilic peptide for membrane penetration and hyaluronic acid for cluster determinant 44 (CD44) targeting was fabricated. Triggered by the external stimuli of laser and US irradiation, their photo/sonothermal performance, in vitro reactive oxygen species (ROS) production capability and tumor-targeting efficiency have been systematically evaluated. It was interestingly found that the external stimulus of laser irradiation induced a greater quantity of ROS, which resulted in significant cell apoptosis and tumor growth inhibition in the presence of ICG@PEP@HA. The individual analyses and corresponding rationales have been investigated. Meanwhile, these hybrid nanomicelles were administered into MDA-MB-231 tumor-bearing nude mice for PDT and SDT therapies and their biocompatibility assessment, and a prevailing PDT efficacy and reliable bio-safety have been evidenced based on the hematological analysis and histochemical staining. In summary, this study has validated a novel pathway to utilize these hybrid nanomicelles for laser/US-triggered localized tumor treatment, and the treatment efficiency may be leveraged by different external stimuli sources. It is also expected to give rise to full accessibility to clinical translations for human cancer treatments by means of the as-reported laser/US-nanomicelle combination strategy.

Surgical resection is the first-line therapy for breast cancer. However, residual tumor cells and the highly immunosuppressive tumor microenvironment (TME) continue to have a serious impact on tumor recurrence and metastasis postresection. Implantation of an in situ hydrogel system postresection has shown to be an effective treatment with great clinical potential. Herein, an injectable zwitterionic hydrogel system was developed for local drug delivery with enhanced immune activation and prevention of tumor recurrence. Driven by electrostatic interactions, poly(sulfobetaine methacrylate) (PSBMA) self-assembles into a hydrogel in saline, achieving low protein adsorption and tunable biodegradability. The chemotherapy drug doxorubicin (DOX) was loaded into copper peroxide nanoparticles (CuO 2 /DOX), which were coated with macrophage membranes to form tumor-targeting nanoparticles (M/CuO 2 /DOX). Next, M/CuO 2 /DOX and the stimulator of interferon genes (STING) agonist 2',3'-cGAMP were coloaded into PSBMA hydrogel (Gel@M/CuO 2 /DOX/STING). The hydrophilic STING agonist was first released by diffusion from hydrogel to activate the STING pathway and upregulate interferon (IFN) signaling related genes, remodeling the immunosuppressive TME. Then, M/CuO 2 /DOX targeted the residual tumor cells, combining with DOX-induced DNA damage, immunogenic tumor cell death, and copper death. Hence, this work combines chemodynamic therapy with STING pathway activation in TME, encouraging residual tumor cell death, promoting the maturation of dendritic cells, enhancing tumor-specific CD8 + T cell infiltration, and preventing postoperative recurrence and metastasis.

The global burden of cancer is increasing rapidly, and nanomedicine offers promising prospects for enhancing the life expectancy of cancer patients. Janus nanoparticles (JNPs) have garnered considerable attention due to their asymmetric geometry, enabling multifunctionality in drug delivery and theranostics. However, achieving precise control over the self-assembly of JNPs in solution at the nanoscale level poses significant challenges. Herein, a low-temperature reversed-phase microemulsion system was used to obtain homogenous Mn 3 O 4 -Ag 2 S JNPs, which showed significant potential in cancer theranostics. Structural characterization revealed that the Ag 2 S (5-10 nm) part was uniformly deposited on a specific surface of Mn 3 O 4 to form a Mn 3 O 4 -Ag 2 S Janus morphology. Compared to the single-component Mn 3 O 4 and Ag 2 S particles, the fabricated Mn 3 O 4 -Ag 2 S JNPs exhibited satisfactory biocompatibility and therapeutic performance. Novel diagnostic and therapeutic nanoplatforms can be guided using the magnetic component in JNPs, which is revealed as an excellent T 1 contrast enhancement agent in magnetic resonance imaging (MRI) with multiple functions, such as photo-induced regulation of the tumor microenvironment via producing reactive oxygen species and second near-infrared region (NIR-II) photothermal excitation for in vitro tumor-killing effects. The prime antibacterial and promising theranostics results demonstrate the extensive potential of the designed photo-responsive Mn 3 O 4 -Ag 2 S JNPs for biomedical applications.

Ferric phosphate (FePOs) nanoenzymes can express peroxidase (POD) activity under the dual stimulation of an acidic environment and high H 2 O 2 concentrations. In living organisms, this generates reactive oxygen species (ROS) in sites of lesion infection, and thus FePOs nanoenzymes can act as antimicrobial agents. Here, CeO 2 and ZnO 2 were immobilized in a scallop-type FePOs nanoenzyme material loaded with a photosensitizer, indocyanine green, to synthesize a multifunctional cascade nanoparticle system (FePOs-CeO 2 -ZnO 2 -ICG, FCZI NPs). H 2 O 2 concentrations could be adjusted through the ZnO 2 self-activation response to the slightly acidic environment in biofilms, further promoting the release of ROS from the POD-like reaction of FePOs, achieving amplification of oxidative stress, DNA and cell membrane damage, and exploiting the photodynamic/photothermal effects of indocyanine green to enhance the antibiofilm effects. CeO 2 can remove redundant ROS by switching from Ce 4+ to Ce 3+ valence, enhancing its ability to fight chronic inflammation and oxidative stress and thus promoting the regeneration of tissues around infection. By maintaining the redox balance of normal cells, increasing ROS at the infection site, eliminating redundant ROS, and protecting normal tissues from damage, the synthesized system maximizes the elimination of biofilms and treatment at the infection site. Therefore, this work may pave the way for the application of biocompatible nanoenzymes.

Triple-negative breast cancer (TNBC) is one of the most aggressive cancers with an immunosuppressive microenvironment, and achieving a satisfactory effect from monotherapies, such as chemotherapy, photodynamic therapy (PDT) or immunotherapy, remains difficult. To solve this puzzle, a deepening synergistic therapy strategy of DNA damage and immunogenic cell death (ICD) stimuli was proposed. We engineered a doxorubicin (DOX) and 4-(hydroxymethyl) phenylboronic acid pinacol ester (PBAP) prodrug polymer, and encapsulated chlorin e6 (Ce6) to obtain the hyaluronidase (HAase) and H 2 O 2 dual-sensitive responsive nanoparticles (Ce6/HDP NPs). The NPs displayed efficient intratumoral accumulation and cellular internalization properties due to the active targeting of the hyaluronic acid (HA). The dual DNA damage of the chemotherapy and ROS production directly caused tumor cell apoptosis. The strong ICD stimuli, which were induced by ROS production and GSH depletion, generated an amplified immunogenicity to activate tumor immunotherapy in vivo . In this manner, the NPs could significantly inhibit primary tumor, abscopal tumor, pulmonary metastasis and recurrent tumor in a subcutaneous 4T1 tumor model, with effective biosafety. This study has provided a promising deepening synergistic therapy strategy against TNBC.

The intelligent responsive drug delivery system has great application potential in cancer precision therapy. Although many antitumor methods have been developed based on drug delivery systems, most of them yet suffer from poor antitumor efficiency. In this project, a near-infrared and pH dual-response multimodal collaborative platform for diagnosis and treatment (PCN-DOX@PDA) was constructed. We used PCN-600 as a vehicle loaded with antineoplastic drugs and polydopamine (PDA). Under 633 nm laser irradiation, the ligand tetrakis(4-carboxyphenyl)porphyrin (TCPP) in PCN-600 can generate singlet oxygen ( 1 O 2 ) and kill tumor cells. PDA is used as photothermal agent of PTT. PCN-DOX@PDA achieves the intelligent release of antitumor drugs by responding to the weak acidity of the tumor microenvironment and thermal stimulation generated by NIR irradiation. In addition, since the central ion of PCN is Fe 3+ , PCN-DOX@PDA realizes the diagnosis and treatment of tumors through magnetic resonance imaging-mediated tumor chemotherapy and photothermal and photodynamic synergistic therapy. This triple synergistic strategy showed excellent biocompatibility and antitumor ability in in vivo experiments on a 4T1 tumor-bearing mouse model, indicating that PCN-DOX@PDA has a good development prospect in the field of precision cancer therapy and diversified biomedical applications.

Ocular formulations should provide an effective antibiotic concentration at the site of infection to treat bacterial eye infections. However, tears and frequent blinking accelerate the drug clearance rate and limit drug residence time on the ocular surface. This study describes a biological adhesion reticulate structure (BNP/CA-PEG) consisting of antibiotic-loaded bioadhesion nanoparticles (BNP/CA), with an average 500-600 nm diameter, and eight-arm NH 2 -PEG-NH 2 for local and extended ocular drug delivery. This retention-prolonging effect is a function of the Schiff base reaction between groups on the surface of BNP and amidogen on PEG. BNP/CA-PEG showed significantly higher adhesion properties and better treatment efficacy in an ocular rat model with conjunctivitis in comparison to non-adhesive nanoparticles, BNP, or free antibiotics. Both in vivo safety experiment and in vitro cytotoxicity test verified the biocompatibility and biosafety of the biological adhesion reticulate structure, indicating a promising translational prospect for further clinical use.

Application of Combined photodynamic therapy (PDT) and photothermal therapy (PTT) has become one of the most promising strategy to replace antibiotics and avoid the epidemic of drug-resistant strains during wound healing. However, high amount of reactive oxygen species (ROS) and high temperature cause severe stress response to normal tissues, leading to potential risks of wound healing. Herein, a three-dimension chitosan hydrogel melanin-glycine-C60 nanoparticles (MGC NPs) were prepared to realized effective anti-bacterial activity, immune activation and macrophage autophagy promotion in three-dimensional wound space without triggering stress response. MGC NP is a composite polymer material composed of natural melanin polymer, oligopeptide and carbon-based material, which showed excellent biological safety. By regulating the peptide length between melanin and C60 and nanoparticle content, a high ROS/heat environment at the upper wound site and a low ROS/heat environment at the lower region adjacent to the wound tissue were established to obtain a three-dimension hydrogel with precise PDT and PTT efficiency in different regions. Highly effective PDT/PTT was used to kill microorganisms in upper region, thus providing a barrier to reduce microbial infection. Mild PDT/PTT in lower region promoted the polarization of M1 macrophage to M2 macrophage and activated autophagy of M2 macrophages, regulating the immune microenvironment and promoting wound repair. In conclusion, the novel three-dimensional PDT/PTT therapy based on natural macromolecules proposed in this study accelerates wound healing through dual pathways on the premise of avoiding wound stress response, which is of great significance for the development of clinical strategies for phototherapy., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

Malignant ascites (MA) is a common symptom of peritoneal metastasis in liver cancer. Cancer immunotherapy can modulate immune cells to induce antitumor immune efficiency. Reprogramming tumor immune microenvironment (TIME) is a momentous strategy to overcome immunosuppression and achieve immune functional normalization. Inspired by the inherent apoptotic bodies and vesicles, we proposed and systematically studied engineered apoptosis-bioinspired nanoparticles (EBN) for cancer immunotherapy of MA. Using both in vitro and in vivo experimental validations, we elucidated that EBN could be efficiently engulfed by the tumor-associated macrophages (TAMs) and manipulate their polarization. Moreover, a boosted immune cascade response as a result of heightening cytotoxic T-lymphocytes (CTLs) activity was investigated. Based on these results, EBN was confirmed to have strong immune cascade activation capability. Remarkably, the injection of EBN further reduced ascites volume and reformed immune cell subtypes, compared to the injection of either PBS or free TMP195 alone. In short, this novel nanodrug delivery system (NDDS) represents a prospective immunotherapeutic approach for clinical therapeutics of hepatoma ascites and other malignant effusion.

Fluorescence bioimaging based on rare-earth-doped nanocrystals (RENCs) in the shortwave infrared (SWIR, 1000-3000 nm) region has aroused intense interest due to deeper penetration depth and clarity. However, their downshifting emission rarely shows sufficient brightness beyond 1600 nm, especially in NIR-IIc. Here, we present a class of thulium (Tm) self-sensitized RENC fluorescence probes that exhibit bright downshifting luminescence at 1600-2100 nm (NIR-IIb/c) for in vivo bioimaging. An inert shell coating minimizes surface quenching and combines strong cross-relaxation, allowing LiTmF 4 @LiYF 4 NPs to emit these intense downshifting emissions by absorbing NIR photons at 800 nm (large Stokes shift ~1000 nm with a absolute quantum yield of ~14.16%) or 1208 nm (NIR-II in and NIR-II out ). Furthermore, doping with Er 3+ for energy trapping achieves four-wavelength NIR irradiation and bright NIR-IIb/c emission. Our results show that Tm-based NPs, as NIR-IIb/c nanoprobes with high signal-to-background ratio and clarity, open new opportunities for future applications and translation into diverse fields., (© 2023. The Author(s).)

Photodynamic therapy (PDT) is a minimally invasive and locally effective treatment method, which has been used in the clinical treatment of a variety of superficial tumors. In recent years, PDT has received extensive attention due to its induction of immunogenic cell death (ICD). However, the repair mechanism of tumor cells and low immune response limit the further development of PDT. To this end, a multifunctional biomimetic nanoplatform 4T1Mem@PGA-Ce6/Ola (MPCO) is developed to co-deliver the photosensitizer Chlorin e6 (Ce6) and Olaparib (Ola) with the function of preventing DNA repair. The nanoplatform shows efficient tumor targeting and cellular internalization properties due to cell membrane camouflage, and Ce6 and Ola produce a significant synergistic anti-tumor effect under laser irradiation. Meanwhile, the nanoplatform can also activate the cyclic guanosine monophosphate-adenosine monophosphate synthase-interferon gene stimulator signaling (cGAS-STING) pathway to produce cytokines. The damage-associated molecular patterns induced by ICD can work with these cytokines to recruit and stimulate the maturation of dendritic cells and induce the systemic anti-tumor immune response. Overall, this multifunctional biomimetic nanoplatform integrating PDT, chemotherapy, and immunotherapy is highlighted here to boost anti-tumor therapy. STATEMENT OF SIGNIFICANCE: Self-repair of DNA damage is the most important reason for the failure of primary tumor eradication and the formation of secondary and metastatic tumors. To address this issue, a multifunctional biomimetic nanoplatform 4T1Mem@PGA-Ce6/Ola (MPCO) was developed to integrate a photosensitizer Chlorine a6 and a poly (ADP-ribose) polymerase inhibitor Olaparib. With tumor targeting ability and controlled release of drugs, the MPCO was expected to enhance tumor immunogenicity and facilitate antitumor immunity through the induction of immunogenic cell death as well as the activation of the cGAS-STING pathway. This study develops a promising combination strategy against tumors and has substantial implications for the prognosis of patients with breast cancer., 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 © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Ligand exchange is fundamentally related to the surface chemistry of nanoparticles in solution and is also an essential procedure for their synthesis and solution processing. The solution of ligand-bearing nanoparticles can be regarded as a dynamic equilibrium of bound and free ligands depending on the concentration and temperature. The direct experimental calibration of the ligand exchange dynamics relies on the in situ and real-time quantification of bound and free ligands. However, existing analytical strategies are often with limited applicability considering the requirement of special functional groups or the indirect detection of photoluminescence or reaction heat. In this work, we explore diffusion-based methods of solution-state nuclear magnetic resonance (NMR) as a general strategy to probe ligand exchange. Using comprehensive numerical simulations, we show that diffusion NMR with designable time sequences can effectively distinguish bound and free ligands and measure the exchange rate constants from 0.5 to 200 s -1 under typical instrumental settings. These methods are demonstrated experimentally on colloidal CdSe nanocrystal systems with carboxylate or amine ligands whose exchange rates were previously undetectable. The kinetic rate constants, activation energies, and thermodynamic parameters of ligand exchange have been obtained under variable temperature conditions. We expect the diffusion NMR strategies to be generally applicable for calibrating the exchange of organic ligands on various nanoparticle systems.

Due to the complex bloodstream components, tumor microenvironment and tumor heterogeneity, traditional nanoparticles have a limited effect (low drug delivery efficiency and poor penetration to the deeper tumor) on eradicating tumors. To solve these challenges, novel platelet membrane-coated nanoparticles (PCDD NPs) were constructed for combined chemo-photodynamic- and immunotherapy of melanoma. The platelet membrane imparted the PCDD nanoparticles with an excellent long circulation effect and tumor targeting ability, which solved the issues of low drug delivery efficiency. After reaching the tumor cells, it releases the drug-loaded CDD micelles, becoming positively charged and facilitating the deep penetration of tumors. Cytotoxic and apoptosis experiments showed that PCDD nanoparticles have the strongest tumor cell killing ability. Based on the excellent results in vitro , PCDD was used to assess anti-tumor and distal tumor inhibition in rat models. The results revealed that the PCDD combined PDT, immunotherapy and chemotherapy could not only inhibit the primary tumor growth (inhibition rate: 92.0%) but also suppress the distant tumor growth (inhibition rate: 90.7%) and lung metastasis, which is far more effective compared to the commercial Taxotere®. Exploration of the molecular mechanism showed that in vivo immune response induced an increase in positive immune responders, suppressed negative immune suppressors, and established an inflammatory tumor immune environment, leading to excellent results in tumor suppression and lung metastasis. In conclusion, this novel multifunctional PCDD nanoparticle is a promising platform for tumor combined chemotherapy, photodynamic therapy (PDT) and immunotherapy.

Herein, we report an activatable near-infrared (NIR) afterglow theranostic prodrug that circumvents high background noise interference caused by external light excitation. The prodrug can release hydroxycamptothecin (HCPT) in response to the high intratumoral peroxynitrite level associated with immunogenic cell death (ICD), and synchronously activate afterglow signal to monitor the drug release process and cold-to-hot tumor transformation. The prodrug itself is an ICD inducer achieved by photodynamic therapy (PDT). PDT initiates ICD and recruits first-arrived neutrophils to secrete peroxynitrite to trigger HCPT release. Intriguingly, we demonstrate that HCPT can significantly amplify PDT-mediated ICD process. The prodrug thus shows a self-sustainable ICD magnification effect by establishing an "ICD-HCPT release-amplified ICD" cycling loop. In vivo studies demonstrate that the prodrug can eradicate existing tumors and prevent further tumor recurrence through antitumor immune response., (© 2022 Wiley-VCH GmbH.)

Owing to the complementary high spatial resolution and signal-to-noise ratio, the dual-modality imaging technique of photoacoustic imaging (PAI)/the second near-infrared window fluorescence imaging (NIR-II FI) holds great promise for the detection of tumor tissues and sentinel lymph nodes (SLNs). Herein, by developing two aggregation-induced emission luminogens (AIEgens) (C-NTBD and O-NTBD) with benzodithiadiazole as the electron acceptor, PAI/NIR-II FI was applied to the diagnosis and treatment of neuroendocrine neoplasms (NENs) and their SLNs for the first time. Both AIEgens exhibited good PAI properties as well as intense NIR-II fluorescence emission. Among them, C-NTBD nanoparticles (NPs) have better PAI and NIR-II FI performance with maximum absorption at 732 nm and emission peak at 1042 nm. In NENs-bearing nude mice model, after successful preoperative localization of NENs by PAI, NIR-II FI was then used to detect SLNs. Under the NIR-II FI guidance of C-NTBD NPs, an SLN with a diameter of 1 mm located in the chest wall and far away from the primary tumor site was even detected and precisely removed. This dual-modality imaging technology could improve the detection of NENs and the accuracy of intraoperative SLNs dissection, improve patient prognosis, and provide a new strategy for the precise treatment of NENs., 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 © 2022 Elsevier Ltd. All rights reserved.)

To enhance the efficacy of tumor therapy, the collection of functional components into a targeting system shows advantages over most homogeneous materials in inducing apoptosis of cancer cells. The security and targeting of therapeutic agents also require the effect combination of additional components. However, the construction of multifunctional composites in a simple system with intelligent cooperative responsiveness remains a challenge. Herein, a reduced polyanionic cluster (rP 2 W 18 ) bearing the absorption at the near infrared (NIR) II region is used as a core carrier to bind the positively charged doxorubicin hydrochloride (DOX) through ionic interaction. To reduce the physiological toxicity, hyaluronic acid grafting β-cyclodextrin side chains is used to cover the ionic complex through host-guest inclusion to DOX. When the nanocomposite is activated by local laser exposure, the final three-component therapeutic agent is demonstrated to present targeted photothermal conversion capability and chemodynamic activity together with chemotherapy. With the controlled release of DOX under the stimulation of mild acidity in the tumor region and photothermal effect, the exposed rP 2 W 18 is aroused by hydrogen peroxide overexpressed in a tumor microenvironment to produce toxic reactive oxygen species, 1 O 2 . This work presents an opportunity for the development of a nanocomposite in NIR-II photothermal/chemo-therapy and chemodynamic synergistic therapy.

Immunotherapy has received tremendous attention for tumor treatment, but the efficacy is greatly hindered by insufficient tumor-infiltration of immune cells and immunosuppressive tumor microenvironment. The strategy that can efficiently activate cytotoxic T lymphocytes and inhibit negative immune regulators will greatly amplify immunotherapy outcome, which is however very rare. Herein, a new kind of semiconducting polymer (SP) nanoparticles is developed, featured with surface-mimicking protein secondary structure (SPSS NPs) for self-synergistic cancer immunotherapy by combining immunogenic cell death (ICD) and immune checkpoint blockade therapy. The SPs with excellent photodynamic property are synthesized by rational fluorination, which can massively induce ICD. Additionally, the peptide antagonists are introduced and self-assembled into β-sheet protein secondary structures on the photodynamic NP surface via preparation process optimization, which function as efficient lysosome-targeting chimaeras (LYTACs) to mediate the degradation of programmed cell death ligand-1 (PD-L1) in lysosome. In vivo experiments demonstrate that SPSS NPs can not only elicit strong antitumor immunity to suppress both primary tumor and distant tumor, but also evoke long-term immunological memory against tumor rechallenge. This work introduces a new kind of robust immunotherapy agents by combining well-designed photosensitizer-based ICD induction and protein secondary structures-mediated LYTAC-like multivalence PD-L1 blockade, rendering great promise for synergistic immunotherapy., (© 2022 Wiley-VCH GmbH.)

Combating the concentration quenching effect by increasing the concentration of sensitized rare-earth ions in rational design upconversion nanostructure will make it easier to utilize injection energy flux and transfer it to emitters, resulting in improved upconversion luminescence (UCL). We proposed a host-sensitized nanostructure (active core@luminescent shell@inert shell) to improve multiphoton UCL of Tm 3+ based on the LiLnF 4 host. Yb 3+ ions were isolated in the core as energy absorbents, and Tm 3+ was doped in the interior LiYbF 4 host shell. Compared with sandwich structured nanocrystals (Y@Y:Yb/Tm@Y), reverse structure (YbTm@Yb@Y), and fully doped structure (YbTm@YbTm@Y), the proposed structure achieved the highest efficiency of multiphoton UCL and favored a better FRET-based application performance as the Tm 3+ located at an optimized spatial distribution. Furthermore, steady-state and dynamic analysis results demonstrate that by manipulating the spatial distribution of the active ions, excited energy can be tuned to enable multiphoton upconversion enhancement, overcoming the conventional limitations.

Afterglow materials have drawn considerable attention due to their attractive luminescent properties. However, their low-efficiency luminescence in aqueous environment limits their applications in life sciences. Here, we developed a molecular fusion strategy to improve the afterglow efficiency of photochemical afterglow materials. By fusing a cache unit with an emitter, we obtained a blue afterglow system with a quantum yield up to 2.59 %. This is 162 times higher than that achieved with the traditional physical mixing system and more than an order of magnitude larger than that of the covalent coupling system. High-efficiency afterglow nanoparticles were obtained and utilized for bio-imaging with a high signal-to-noise ratio (SNR) of 131, and for the lateral flow immunoassay (LFIA) of β-hCG with a low limit of detection (LOD) of 0.34 mIU mL -1 . This paves a new way for the construction of high-efficiency afterglow materials and expands the number of luminescence reporter candidates for disease diagnosis and bio-imaging., (© 2022 Wiley-VCH GmbH.)

In the search for materials with enhanced near-infrared (NIR) photothermal properties and capability of providing environment-sensitive therapy, a method that combines isolated components into one nanocomposite is developed. The technique simultaneously involves redox, charge-transfer formation, and ionic complexation. During the polyoxophosphomolybdate (PMo) cluster mixing with biosafe chromogen 3,3',5,5'-tetramethylbenzidine (TMB), the reduced state (rPMo) and the oxidized TMB in the state of charge-transfer complex (cTMB) emerge spontaneously. The two reduced and oxidized components with charges form a stable ionic complex that resists physiology, saline, broad pH, and elevated temperature. Both the rPMo and cTMB contribute to the total sustainable photothermal conversion efficiency of 48.4% in the NIR-II region. The ionic complex exhibits biocompatibility in in vitro cell viability evaluation and is demonstrated to enter tumor cells with sustained photothermal property and complexation stability. Due to the local acidity that triggers further interaction among rPMo clusters, a distinct accumulation of the ionic complex at the tumor position is observed after caudal vein injection. Moreover, a remarkable local NIR-II photothermal image appears. The diminishment of tumor in mice with maintained body weight demonstrates the comprehensive effect of this NIR-II photothermal therapeutic material., (© 2022 Wiley-VCH GmbH.)

Photothermal therapy is a promising tumor ablation technique that converts light into heat energy to kill cancer cells. Prussian blue (PB), a biocompatible photothermal reagent, has been widely explored for cancer treatment. However, the translational potential of PB is severely hampered by its low photothermal conversion efficiency (PCE) and poor stability. To tackle these issues, we adopted the biomineralization modality where PB was integrated with calcium phosphate (CaP) through the binding between calcium ions and PB. The mineralized PB (CaP&PB) demonstrated significantly improved PCE (40.2%), resulting from a calcium-induced bandgap-narrowing effect, and exhibited superior suspension stability. Using a 4T1 orthotopic breast cancer BALB/c mouse model, we observed that mineralized PB showed a significant temperature increase within the tumor, which led to better tumoricidal activity compared with CaP and PB when identical NIR treatment was applied. These achievements demonstrated the success of introducing calcium phosphate into Prussian blue by biomineralization to improve the PCE and stability of photothermal reagents, suggesting an alternative translational strategy for enhanced cancer photothermal therapy.

Transcatheter arterial embolization (TAE) is an effective therapeutic method for several clinical ailments. Interminably, the polymer microsphere is reflected as one of the idyllic embolic materials due to the exceptional biocompatibility and microcatheter administration. Herein, a one-step solution drying technique was first developed to fabricate sodium hyaluronate microspheres cross-linked by 1,4-Butanediol diglycidyl ether (BDDE) for transcatheter arterial embolization. The monodispersed sodium hyaluronate microspheres with a diameter range from 350 to 900 μm were obtained by this technique without any complicated instrument and extra surfactant, which is consistent with the standard distribution of commercial embolic microspheres. Additionally, barium sulfate (BaSO 4 ) nanoparticles were introduced as the contrasting mediator to improve the X-ray imaging capability of sodium hyaluronate microspheres and then achieve a real-time trace and discernibility in vivo . A significantly embellished mechanical strength and compressibility for BaSO 4 @SH microspheres were also observed. In vitro biocompatibility evaluation revealed non-cytotoxicity and great hemocompatibility of BaSO 4 @SH microspheres. Moreover, the histopathological analysis and computed tomography images of the embolized kidney confirmed the effective occlude blood and in vivo visibility capability of BaSO 4 @SH microspheres for at least 4 weeks. Conclusively, such an inexpensive and environmentally friendly technique for fabricating BaSO 4 @SH microspheres might be a promising strategy to promote the development of transcatheter arterial embolization in practice.

Limitations in compatibility and effectiveness in delivering bioactive compounds often make it prohibitively difficult to apply Pickering emulsions in wound dressing. In this research, we prepared Pickering emulsion composite hydrogels based on carboxymethyl chitosan - sodium alginate (CMCS-SA) nanoparticles (NPs) stabilized Pickering emulsions, poloxamer 407 (PLX), and curcumin (CUR). CMCS-SA NPs were prepared and used to stabilize Pickering emulsion. The stability of Pickering emulsion improved with the increase of the concentration of NPs, and was highly sensitive to ionic strength change. This Pickering emulsion remained stable at various temperatures. After curcumin were introduced into the emulsion, 0.6% CMCS-SA NPs Pickering emulsion showed controlled release of curcumin in vitro. The CMCS-SA-PLX-CUR hydrogels also exhibited smooth surface and dense structure. This composite hydrogels has antibacterial properties against Escherichia coli and Staphylococcus aureus. Moreover, the CMCS-SA-PLX-CUR hydrogels improved wound healing and increased expression of Ki67 and CD31. RT-qPCR results indicated that the mRNA levels of α-SMA and TGF-β1 in the CMCS-SA-PLX-CUR group were downregulated, while the mRNA levels of TGF-β3 increased. The present study suggests that the potentials of CMCS-SA-PLX-CUR hydrogels are promising in protecting bioactive components and wound care management., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Photodynamic therapy (PDT) has been widely used in tumor therapy due to its high spatial-temporal control and noninvasiveness. However, its clinical application is limited by weak efficacy, shallow tissue penetration, and phototoxicity. Herein, a facile theranostic nanoplatform based on photoswitchable lanthanide-doped nanoparticles was designed. Typically, these nanoparticles had UV-blue and 1525 nm emission upon 980 nm excitation and 1525 nm emission upon 800 nm excitation. We further used these nanoparticles for achieving real-time near-infrared (NIR)-IIb imaging (800 nm) with a high signal-to-noise ratio and imaging-guided PDT (980 nm). Moreover, such a photoswitchable nanoplatform capping with pH-sensitive calcium phosphate for coloading doxorubicin (a chemotherapeutic immunogenic cell death [ICD] inducer) and paramagnetic Mn 2+ ions enhances T 1 -magnetic resonance imaging in the tumor microenvironment. Our results suggest that this theranostic nanoplatform could not only kill tumor cells directly through dual-modal image-guided PDT/chemotherapy but also inhibit distant tumor and lung metastasis through ICD. Therefore, it has great potential for clinical application .

Acute lung injury (ALI) is a disease associated with suffering and high lethality, but to date without any effective pharmacological management in the clinic. In the pathological mechanisms of ALI, a strong inflammatory response plays an important role. Herein, based on macrophage 'homing' into inflammation sites and cell membrane coating nanotechnology, we developed a biomimetic anti-inflammation nanosystem (MM-CEP/NLCs) for the treatment of ALI. MM-CEP/NLCs were made with nanostructured lipid carriers (NLCs) coated with natural macrophage membranes (MMs) to achieve effective accumulation of cepharanthine (CEP) in lung inflammation to achieve the effect of treating ALI. With the advantage of suitable physicochemical properties of NLCs and unique biological functions of the macrophage membrane, MM-CEP/NLCs were stabilized and enabled sustained drug release, providing improved biocompatibility and long-term circulation. In vivo , the macrophage membranes enabled NLCs to be targeted and accumulated in the inflammation sites. Further, MM-CEP/NLCs significantly attenuated the severity of ALI, including lung water content, histopathology, bronchioalveolar lavage cellularity, protein concentration, and inflammation cytokines. Our results provide a bionic strategy via the biological properties of macrophages, which may have greater value and application prospects in the treatment of inflammation.

Dysfunction of the calcium balancing system and disruption of calcium distribution can induce abnormal intracellular calcium overload, further causing serious damage and even cell death, which provides a potential therapeutic approach for tumor treatment. Herein, a nano-platform, which includes UCNPs-Ce6@RuR@mSiO 2 @PL-HA NPs (UCRSPH) and SA-CaO 2 nanoparticles, is prepared for improving the tumor micro-environment (TME), Ca 2+ signal disturbance as well as enhanced photodynamic tumor therapy (PDT). UCRSPH combined with SA-CaO 2 can alter TME and relieve hypoxia of the tumor to realize self-reinforcing PDT under near-IR irradiation (980 nm). The ruthenium red (RuR) in the UCRSPH NPs can be released to the cytoplasm after endocytosis of the nanoparticles, target Ca 2+ channel proteins on the endoplasmic reticulum and mitochondria, sarcoplasmic reticulum Ca 2+ -ATPase (SERCA), and mitochondrial calcium uniporter (MCU). The combined participation of nanoparticles and RuR promotes Ca 2+ imbalance and cytoplasmic calcium overload with the assistance of CaO 2 , and provides tumor cells higher sensitivity to PDT. Furthermore, the nano-platform also provides fluorescence imaging and calcification computed tomography imaging for in vivo treatment guidance. In conclusion, this image-guided nano-platform show potential for highly specific, efficient combined therapy against tumor cells with minimal side-effects to normal cells by integrating TME improvement, self-reinforcing PDT, and Ca 2+ signal disturbance., (© 2021 Wiley-VCH GmbH.)

The combination of photodynamic therapy (PDT) and photothermal therapy (PTT) has emerged as a promising strategy for complete tumor ablation therapy. Herein, a boron dipyrromethene (BODIPY)-conjugated hyaluronic acid polymer that can self-assemble to form the nanoparticles (BODIPY-HA NPs) was prepared for combined cancer PDT and PTT. The fluorescence emission and reactive oxygen species (ROS) generation of BODIPY-HA NPs were inhibited because of the π-π stacking behavior of BODIPY, resulting in photothermal effect under 808 nm light irradiation. Upon the internalization by cancer cells, the BODIPY-HA NPs could disassemble into BODIPY-HA molecules, with the recovery of the fluorescence and ROS generation for PDT. Importantly, in vitro results confirmed that combined PTT and PDT have exhibited better anticancer effect than PTT alone upon 808 nm laser irradiation. These results showed that the self-assembled BODIPY-HA NPs may be a promising nanomedicine for synergistic cancer PDT and PTT.

Nitric oxide (NO) gas treatment offers a promising strategy for tumor therapy; however, its practical application is still limited due to its poor efficacy and biotoxicity which were caused by gas leakage during blood delivery. Herein, a nano-platform (CMH-OBN) composed of chlorin e6-melanin-hyaluronic acid nanoparticles (Ce6-MNP-HA, CMH) and oxidized bletilla striata polysaccharide microcapsules (Oxi-BSP) carrying NO donors was prepared for responsive and cascaded release of NO, reactive oxygen species (ROS) and its secondary metabolite reactive nitrogen species (RNS) in tumor sites. Melanin not only endowed CMH with good photothermal properties, but also helped Ce6 to produce a large number of ROS under near-infrared (NIR) irradiation. OBN microcapsules, which were sensitive to ROS, can release NO donors under the stimulation of ROS released by CMH nanoparticles under NIR irradiation and can further release NO in the tumor microenvironment (TME) with high expression of glutathione (GSH). NO could further up-regulate soluble guanylate cyclase-cyclic guanosine monophosphate (sGC-cGMP) signal pathways to relieve hypoxia, thus further enhancing the photodynamic therapy (PDT). Moreover, the cascaded release of ROS and NO could produce RNS with higher lethality, which could sequentially initiate the cellular apoptotic procedure and promote immunotherapy by activating T cells at the tumor sites. More interestingly, the CMH-OBN nano-platform could supply magnetic resonance imaging (MRI) and infrared photothermal imaging guidance for tumor therapy. In conclusion, the development of a CMH-OBN nano-platform provides a satisfactory demonstration by combining NO therapy with photothermal therapy (PTT), PDT and immunotherapy for the treatment of cancer.

Biosynthesis of nanomaterials has attracted much attention for its excellent characteristics such as low energy consumption, high safety, and environmental friendliness. As we all know, the toxic selenite can be transformed into higher-value nanomaterials by using bacteria. In this study, nano-selenium was synthesized by halophilic Bacillus subtilis subspecies stercoris strain XP in LB medium supplemented with selenite (electron acceptor). The physicochemical characteristics of nano-selenium were analyzed by scanning electron microscope (SEM), X-ray energy dispersive spectral analysis (EDAX), X-ray diffraction (XRD), and fourier transform infrared spectroscopy (FTIR). Meanwhile, the antifungal activity of nano-selenium to strawberry pathogens (fusarium wilt, erythema, and purple spot fungi) was determined. The products from reduction of selenite by strain XP was amorphous spherical selenium nanoparticles (SeNPs) with a diameter range of 135-165 nm. The production of SeNPs was positively correlated with time (0-48 h) and no changes were observed on cell morphology. Selenium was dominant in the surface of SeNPs where the organic elements (C, O, N, and S) existed at the same time. SeNPs were coated with biomolecules containing functional groups (such as -OH, C=O, N-H, and C-H) which were associated with the stability and bioactivity of particles. Although the highest concentration of SeNPs had significant (P<0.05) inhibitory effects on three strains of strawberry pathogens, antifungal activity to erythema and fusarium wilt pathogenic fungi was higher than that to purple spot pathogenic fungi from strawberry. In conclusion, strain XP not only has strong tolerance to high salt stress, but can be also used to synthesize biological SeNPs with good stability and biological activity. Thus, the strain XP has bright perspectives and great potential advantage in pathogens control and green selenium-rich strawberry planting as well as other fields.

The development of activatable photosensitizers (PSs) is of particular interest for achieving tumor photodynamic therapy (PDT) with minimal side effects. However, the in vivo applications of PSs are limited by complex physiological and biological delivery barriers. Herein, boron dipyrromethene (BDP)-based nanoparticles are developed through the self-assembly of a multifunctional "one-for-all" building block for enhanced tumor penetration and activatable PDT. The nanoparticles show excellent colloidal stability and long circulation lifetime in blood. Once they reach the tumor site, the first-stage size reduction occurs due to the hydrolysis of the Schiff base bond between polyethylene glycol and the cyclic Arg-Gly-Asp peptide in the acidic tumor microenvironment (pH~6.5), facilitating tumor penetration and specific recognition by cancer cells overexpressing integrin α ν β 3 receptors. Upon the endocytosis by cancer cells, the second-stage size reduction is triggered by more acidic pH in lysosomes (pH~4.5). Importantly, the protonated diethylamino groups can block photoinduced electron transfer from the amine donor to the excited PSs and accelerate complete disassembly of the nanoparticles into single PS molecule, with the recovery of the fluorescence and photoactivity for efficient PDT. This study presents a smart PS delivery strategy involving acidity-triggered hierarchical disassembly from the nano to molecular scale for precise tumor PDT., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In this study, we recruited chitosan (CS) both for selenium nanoparticles (SeNPs) synthesis and for the development of a thermoresponsive nanocomposite hydrogel with the addition of glycerol phosphate (GP). Considering that SeNPs are toxic at high concentrations, five different ingredients of the nanocomposite hydrogel system with low concentrations of SeNPs (1.25-20 μg/mL) were prepared. The gelation conditions, structural characteristics, and mechanical properties of SeNPs-loaded thermosensitive CS/GP hydrogels were investigated. We also evaluated their antioxidizing activities and biocompatibility of the CS/GP/SeNPs hydrogels. Our study demonstrated that the incorporation of SeNPs in the hydrogel improved its mechanical properties, antioxidant activity, and degree of swelling. According to the properties of SeNPs and CS/GP thermosensitive hydrogels, the combination of these two technologies in an appropriate manner would be a promising antioxidant system for drug delivery and tissue engineering.

The application of Prussian blue analogue nanoparticles in anaerobic digestion was firstly used to evaluate the removal effect of ammonia nitrogen inhibition in anaerobic digestion. We have successfully prepared Prussian blue analogue nanoparticles, which has a high adsorption capacity of ammonia nitrogen in anaerobic digestion is 71.09 mg/g. The high concentration anaerobic digestion of rural organic household waste was not successful because of the serious inhibition of ammonia nitrogen. After adding Prussian blue analogue nanoparticles, the methane production of each group increased greatly, up to 302.22 ml/gVS. The concentration of ammonia nitrogen in anaerobic digestion decreased to 1700.77 mg/l. Prussian blue analogue nanoparticles have a good application prospect in high concentration anaerobic digestion of rural organic household waste enriched with a high concentration of ammonia nitrogen., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Dental implants are the most innovative and superior treatment modality for tooth replacement. However, titanium implants still suffer from insufficient antibacterial capability and peri-implant diseases remain one of the most common and intractable complications. To prevent peri-implant diseases, a composite coating containing a new antibacterial agent, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone (BBF) was fabricated on titanium. This study was designed to investigate the antibacterial activity of the composite coating against two common peri-implant pathogens ( Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans ). The morphology of the composite coating showed that BBF-loaded poly(L-lactic acid) nanospheres were well-distributed in the pores of the microarc oxidation coating, and cross-linked with each other and the wall pores by gelatin. A release study indicated that the antibacterial coating could sustain the release of BBF for 60 d, with a slight initial burst release occurring during the first 4 h. The antibacterial rate of the composite coating for adhering bacteria was the highest (over 97%) after 1 d and over 90% throughout a 30-day incubation period. The total fluorescence intensity of the composite coating was the lowest, and the vast majority of the fluorescence was red (dead bacteria). Moreover, real-time polymerase chain reaction analysis confirmed that the relative gene expression of the adherent bacteria on the composite coating was down-regulated. It was therefore concluded that the composite coating fabricated on titanium, which showed excellent and relatively long-term antibacterial activity against Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans , is a potential and promising strategy to be applied on dental implants for the prevention of peri-implant diseases.

Background: Asthma has been regarded as an inflammatory disease, and group 2 innate lymphoid cells (ILC2s) are implicated in asthma pathogenesis. However, no strategy is available to block ILC2s function. Efficiency is also limited due to the use of systemic or subcutaneous routes of administration. The purpose of this study was to investigate the effects of nanoparticles targeting suppression of tumorigenicity 2 (ST2), which is the ILC2 receptor, to alleviate lung inflammation in the murine model of asthma., Methods: The ultra-small SPIO nanoparticles were firstly synthesized, OVA-induced mice were administered by anti-ST2-conjugated nanoparticles. The inflammatory degree of the lung was investigated by H&E. The percentages of ILC2s and CD4 + T cells in bronchoalveolar lavage fluid (BALF) and lung tissue were determined by FACS. Th2-cytokine and OVA-IgE levels were detected by real-time PCR and ELISA, respectively., Results: Treatment with anti-ST2-conjugated nanoparticles significantly alleviated airway inflammation, IL-33 and IL-13 levels and the percentage of CD4 + T cells. The percentage of ILC2s was increased, whereas the levels of IL-13 and IL-5 expressed by ILC2s were reduced., Conclusion: In the present study, we demonstrated that anti-ST2-conjugated nanoparticles can efficiently control lung inflammation in OVA-induced mice by reducing the ability of ILC2s to produce IL-5 and IL-13, thereby reducing CD4+T cells. Our study also demonstrated that the nanoparticle delivery system could improve the performance of anti-ST2, which may be used as a strategic tool to expand the current drug market., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Wu et al.)

Bone regeneration is a complex process in which angiogenesis and osteogenesis are crucial. Introducing multiple angiogenic and osteogenic cues simultaneously into a single system and tuning these cues to optimize the niche remains a challenge for bone tissue engineering. Herein, based on our injectable biomimetic hydrogels composed of silk nanofibers (SNF) and hydroxyapatite nanoparticles (HA), deferoxamine (DFO) and bone morphogenetic protein-2 (BMP-2) were loaded on SNF and HA to introduce more angiogenic and osteogenic cues. The angiogenesis and osteogenesis capacity of injectable hydrogels could be regulated by tuning the delivery of DFO and BMP-2 independently, resulting in vascularization and bone regeneration in cranial defects. The angiogenesis and osteogenesis outcomes accelerated the regeneration of vascularized bones toward similar composition and structure to natural bones. Therefore, the multiple biophysical and chemical cues provided by the nanofibrous structures, organic-inorganic compositions, and chemical and biochemical angiogenic and osteogenic inducing cues suggest the potential for clinical applicability of these hydrogels in bone tissue engineering.

Bladder cancer, with the highest recurrence rate in all malignancy, is a common urologic cancer that arises on the bladder mucosa. Currently, tumor resection followed by intravesical chemotherapy is the primary treatment of bladder cancer, which has limited effectiveness ascribe to short dwell-time of intravesical drugs in bladder. Therefore, there is a need to develop mucoadhesive and sustained drug delivery systems to increase drug residence time for intravesical chemotherapy. In this study, poly(amidoamine) (PAMAM) dendrimers were modified onto the surface of mesoporous silica nanoparticles (MSNPs) through a layer-by-layer grafting method. A series of PAMAM-modified MSNPs were prepared and compared for their mucoadhesive capabilities on pig bladder wall and controlled drug release properties. Results demonstrated an increase in the mucoadhesive capacity of PAMAM-modified MSNPs upon an increase in the number of PAMAM amino groups, and the maximum nanoparticle mucoadhesivity was observed after two-generation PAMAM were grafted on the surface of MSNPs. An antineoplastic, doxorubicin, was encapsulated in the mesopores of PAMAM-modified MSNPs, and the drug-loaded nanoparticles can provide a sustained drug release triggered by acidic pH. The present study demonstrates that the mucoadhesive and drug release properties of MSNPs can be controlled by the layer number of PAMAM dendrimers on the nanoparticle surface, holding significant potential for the development of mucoadhesive drug delivery systems for bladder cancer therapy., 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 © 2020 Elsevier B.V. All rights reserved.)

MicroRNAs (miRNAs) therapy has shown to have great promise for the treatment of androgen-independent prostate cancer (AIPC) due to the low efficiency of hormonal therapy. However, instability of RNA and inefficiency of RNA therapy limit the use of miRNAs in the treatment of AIPC. Here, we report a pH/ATP-activated nanocomplexes for increasing cytosolic delivery of miR146a which can effectively inhibit the expression of epidermal growth factor receptor (EGFR) in AIPC. The nanocomplexes show identical suppressing effect in invasion, colony formation, migration ability, and growth of DU145 cells compared with Lipofectamine 2000 (lipo). But for in vivo experiments, the nanocomplexes vigorously suppress the growth of tumor volumes comparing to lipo group after five weeks' treatment. These results demonstrate the potential of the pH/ATP-activated nanocarriers for AIPC gene therapy.

Breast cancer metastases to bone poses a significant challenge for the administration of treatment strategies. The bone microenvironment, metastatic tumor cells, osteoclasts, and tumor-associated macrophages (TAMs) all play crucial and synergistic roles in creating a favorable environment for the proliferation, progression, and survival of the metastatic tumor, which in turn induces osteoclast-mediated bone destruction. In this study, we functionalized immunostimulatory cytosine-phosphate-guanosine (CpG)-loaded metal-organic framework (MOF) nanoparticles with bone targeting capabilities by surface modification with FDA approved antiresorptive bisphosphonate, zoledronic acid (ZOL). The functionalized bone targeting immunostimulatory MOF (BT-isMOF) nanoparticles demonstrates strong binding to calcium phosphate in vitro and exhibits specific targeting and accumulation in bone tissues in vivo. In vitro cellular and biochemical analyses demonstrated that the BT-isMOF nanoparticles could potently inhibit osteoclast formation and concomitantly induce macrophages polarization toward the M1 pro-inflammatory phenotype. Finally, using the intratibial murine model of breast cancer bone metastasis, we showed that the administration of BT-isMOF nanoparticles significantly suppressed osteoclast-mediated bone destruction and enhanced polarization of tumor-resident macrophages to M1 phenotype. Together, our data provides promising evidence for the potential therapeutic application of the BT-isMOF nanoparticles in the treatment of breast cancer bone metastases.

Herein, a novel photothermal agent based on polyoxometalate clusters and food-borne antioxidant peptides was exploited to overcome the inherent problems of poor photothermal stability of polyoxometalate photothermal materials, which commonly appear in the current stage of development, and the inevitable simultaneous inflammatory responses during the therapeutic process.

Background: Cancer, as one of the most dangerous disease, causes millions of deaths every year. The main reason is the absence of an effective and thorough treatment. Drug delivery systems have significantly reduced the side-effect of chemotherapy. Combined with nanotechnology, smart drug delivery systems including many different nanoparticles can reduce the side-effect of chemotherapy better than traditional drug delivery systems., Methods: In this article, we will describe in detail the different kinds of nanoparticles and their mechanisms emphasizing the triggering factors in drug delivery. Besides, the application of smart drug delivery systems in imaging will be introduced., Results: Combined with nanotechnology, smart drug delivery systems including many different nanoparticles can reduce the side-effect of chemotherapy better than traditional drug delivery systems., Conclusion: Despite considerable progress in nanoparticle research over the past decade, such as smart drug delivery systems for the treatment of cancer, molecular imaging probes and the like. The range of nanoparticles used in multifunction systems for imaging and drug delivery continues to grow and we expect this dilatation to continue. But to make nanoparticles truly a series of clinical products to complement and replace current tools, constant exploration efforts and time are required. Overall, the future looks really bright., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

To realize surfactant-free synthesis of biomass-derived hollow mesoporous carbon spheres and their derivatives, choice of synthetic methodology and carbon precursor is crucial. Herein, a brand-new hollow mesoporous carbon sphere (HMCS) is first synthesized from 8-quinolinol modified chitosan via an in situ stöber templating approach without surfactant followed by pyrolysis and alkali washing. The resultant HMCS is uniform, and shows a cavity size of 417 nm, a shell thickness of 5 nm, and a narrow mesopore size distribution centered at 3.9 nm. The HMCS is then upgraded by encapsulation of a single Au nanocrystal (NC) into the void of HMCS to form a yolk-shell architecture, YS-Au@HMCS. Its cavity size and shell thickness are decreased to 187 and 3 nm, while the mesopore size is increased to 4.3 nm, the surface area (215 m 2  g -1 ) and mesoporosity (74.7%) are triple and twice that of HMCS, respectively, just by halving the delay time of carbon source addition. Owing to the unique hollow interiors and mesopores, as well as their synergism with the encapsulated Au NCs, the elaborately fabricated YS-Au@HMCS exhibits appealing catalytic performances towards the deposal of sewage. It delivers a large activity factor of 34.32, 13.29 and 0.05 s -1  g -1 in the reduction of 4-nitrophenol and methylene blue using sodium borohydride, and in the photodegradation of methylene blue under visible light irradiation, respectively. These advances shed new light on the synthesis of hollow mesoporous carbon spheres and the designed synthesis of functional carbon materials with versatile applications., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study identifies the phototoxic potential of commercial titanium dioxide nanoparticles (TiO 2 NPs) used in sunscreens and consumer products by employing a tiered testing approach comprising physicochemical, in vitro and ex vivo tests. Our results revealed that all the test samples of TiO 2 NPs, varied in surface coating, crystallinity and primary particle size, produced hydroxyl radicals upon UVA photoexcitation as determined by electron spin resonance (ESR) spectroscopy. Their phototoxic potentials were assessed first by combining the validated 3T3 neutral red uptake phototoxicity test and red blood cell phototoxicity test and subsequently in ex vivo models of chick chorioallantoic membrane (CAM) and reconstructed human 3D skin model (H3D). Crystalline structure and particle size of TiO 2 NPs were found to exert a major influence on the photocatalytic activity and the associated phototoxic effects. Besides, a medium-sized sample with silica/alumina also exhibited high phototoxic potency with no obvious relevance to the enhanced hydroxyl radicals and lipidperoxidation. This effect might be taken place through the interaction of harmful metal ions released from the oxide coating. However, no phototoxicity was observed on a H3D skin model probably due to the lack of efficient percutaneous absorption of TiO 2 NPs. This study demonstrates the efficacy of a tiered testing strategy for identifying phototoxic hazards of TiO 2 NPs and suggests the need for a comprehensive assessment that takes account of the effects of different coating materials and potential interactions between multiple mechanisms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Multimodality imaging-guided therapy based on lanthanide-doped upconversion nanoparticles (UCNPs) has become a trend in cancer theranostics. However, the overheating effect of 980 nm excitation in photodynamic therapy (PDT) and the difficulties in optimizing multimodality imaging integration within a single particle are still challenges. Herein, 800 nm driven NaErF4@NaLuF4 UCNPs have been explored for optimized multimodality imaging and near-infrared (NIR) triggered PDT. Our results confirmed that the optimal ∼5 nm shell thickness can well balance the enhancement of upconversion luminescence and the attenuation of energy transfer efficiency from Er3+ towards a photosensitizer, to achieve efficient production of singlet oxygen (1O2) for PDT under 800 nm excitation. Furthermore, the as-obtained NaErF4@NaLuF4 UCNPs showed effective and applicable performance for upconversion luminescence (UCL) imaging, X-ray computed tomography (CT), and high-field T2 magnetic resonance imaging (MRI). This nanomaterial can serve as an excellent theranostic agent for multimodality imaging and image-guided therapy.

The multiple physiologic characteristics of glucagon-like peptide 1 (GLP-1) make it a promising drug candidate for treating type 2 diabetes mellitus. However, the half-life of GLP-1 is short as a result of degradation by dipeptidyl peptidase IV and renal clearance. Stabilizing GLP-1 is therefore critical for its use in drug development. Self-assembling peptides are a class of peptides that undergo spontaneous assembly into ordered nanostructures. Recently, studies of self-assembling peptides as drug carriers have increased because of their enhanced stability. In the present study, GLP-1 was modified to incorporate the structural characteristics of self-assembling peptides aiming to generate a self-assembling GLP-1 derivative. Receptor binding capacity and insulinotropic effects were measured to investigate the physiologic functions of GLP-1, along with morphologic approaches to observe supramolecular formation on self-assembly at the nano scale. Finally, blood glucose regulation and body weight were monitored after administration of selected derivatives. Our findings revealed that cadyglp1e and cadyglp1m both exhibited improved stability even though different nanoshapes were observed for these two self-assembling peptides. Both cadyglp1e and cadyglp1m retained glucoregulatory activity after insulin stimulation and were potent drug candidates for long-acting GLP-1 derivatives to treat type 2 diabetes mellitus. Our findings support the feasibility of introducing self-assembly functions into peptides with poor stabilities, such as GLP-1.-Li, Y., Cui, T., Kong, X., Yi, X., Kong, D., Zhang, J., Liu, C., Gong, M. Nanoparticles induced by embedding self-assembling cassette into glucagon-like peptide 1 for improving in vivo stability.

Photoswitchable materials are important in broad applications. Recently appeared inorganic photoswitchable upconversion nanoparticles (PUCNPs) become a competitive candidate to surmount the widespread issue of the organic counterparts -photobleaching. However, current PUCNPs follow solely Yb 3+ /Nd 3+ cosensitizing mode, which results in complex multilayer doping patterns and imperfectness of switching in UV-blue region. In this work, we have adopted a new strategy to construct Nd 3+ free PUCNPs-NaErF 4 @NaYF 4 @NaYbF 4 :0.5%Tm@NaYF 4 . These PUCNPs demonstrate the superior property of photoswitching. A prominent UV-blue emission from Tm 3+ is turned on upon 980 nm excitation, which can be completely turned off by 800 nm light. The quasi-monochromatic red upconversion emission upon 800 nm excitation-a distinct feature of undoping NaErF 4 upconversion system-endows the PUCNPs with promising image-guided photoinduced "off-on" therapy in biomedicine. As a proof-of-concept we have demonstrated the imaging-guided photodynamic therapy (PDT) of cancer, where 800 nm excitation turns off the UV-blue emission and leaves the emission at 660 nm for imaging. Once the tumor site is targeted, excitation switching to 980 nm results in UV-blue emission and the red emission. The former is used to induce PDT, whereas the latter is to monitor the therapeutic process. Our study implies that this upconversion photoswitching material is suitable for real-time imaging and image-guided therapy under temporal and spatial control.

Prostate cancer (PCa) is the most common type of cancer in men with high morbidity and mortality. However, the current treatment with drugs often leads to chemotherapy resistance. It is known that the multi-disciplines research on molecular imaging is very helpful for early diagnosing, staging, restaging and precise treatment of PCa. In the past decades, the tumor-specific targeted drugs were developed for the clinic to treat prostate cancer. Among them, the emerging nanotechnology has brought about many exciting novel diagnosis and treatments systems for PCa. Nanotechnology can greatly enhance the treatment activity of PCa and provide novel theranostics platform by utilizing the unique physical/chemical properties, targeting strategy, or by loading with imaging/therapeutic agents. Herein, this chapter focuses on state-of-art advances in imaging and diagnosing PCa with nanomaterials and highlights the approaches used for functionalization of the targeted biomolecules, and in the treatment for various aspects of PCa with multifunctional nanoparticles, nanoplatforms and nanodelivery system.