Enhancing oncolytic virus efficiency with methionine and N-(3-aminoprolil)methacrylamide modified acrylamide cationic block polymer.

Oncolytic virus ablation of tumor cells has the advantages of high tumor selectivity, strong immunogenicity, and low side effects. However, the recognition and clearance of oncolytic viruses by the immune system are the main factors limiting their anti-tumor efficiency. As a highly biosafe and highly modifiable oncolytic virus vector, acrylamide can improve the long-term circulation of oncolytic viruses. Still, it is limited in its uptake efficiency by tumor cells. Herein, we constructed an N-hydroxymethyl acrylamide-b-(N-3-aminopropyl methacrylamide)-b-DMC block copolymer (NMA-b-APMA-b-DMA, NAD) as an oncolytic virus carrier, which not only improves the long-term circulation of oncolytic viruses in the body but also shows excellent stability for loading an oncolytic virus. The data shows that there was no obvious difference in the transfection effect of the NAD/Ad complex with or without neutralizing antibodies in the medium, which meant that the cationic carrier mediated by NAD/Ad had good serum stability. Only 10 micrograms of NAD carrier are needed to load the oncolytic virus, which can increase the transfection efficiency by 50 times. Cell experiments and mouse animal experiments show that NAD vectors can significantly enhance the anti-tumor effect of oncolytic viruses. We hope that this work will promote the application of acrylamide as an oncolytic virus vector and provide new ideas for methods to modify acrylamide for biomedical applications.

Fabrication of Dual-Functional Bacterial-Cellulose-Based Composite Anion Exchange Membranes with High Dimensional Stability and Ionic Conductivity.

Anion exchange membranes (AEMs) are increasingly becoming a popular research area due to their ability to function with nonprecious metals in electrochemical devices. Nevertheless, there is a challenge to simultaneously optimize the dimensional stability and ionic conductivity of AEMs due to the "trade-off" effect. Herein, we adopted a novel strategy of combining filling and cross-linking using functionalized bacterial cellulose (PBC) as a dual-functional porous support and brominated poly(phenylene oxide) (Br-PPO) as the cross-linking agent and filler. The PBC nanofiber framework together with cross-linking can provide a reliable mechanical support for the subsequent filled polymer, thus improving the mechanical properties and effectively limiting the size change of the final quaternized-PPO (QPPO)-filled PBC composite membrane. The composite membrane showed a very low swelling ratio of only 10.35%, even at a high water uptake (81.83% at 20 °C). Moreover, the existence of multiple -NR3+ groups in the cross-link bonds between BC and Br-PPO can provide extra OH- ion transport sites, contributing to the increase in ionic conductivity. The final membrane demonstrated a hydroxide ion conductivity of 62.58 mS cm-1, which was remarkably higher than that of the pure QPPO membrane by up to 235.93% (80 °C). The successful preparation of the PBC3/QPPO membrane provides an effective avenue to tackle the trade-off effect through a dual-functional strategy.

Composite proton exchange membrane for fuel cells based on chitosan modified by acid-base amphoteric nanoparticles.

Currently, achieving a simultaneous improvement in proton conductivity and mechanical properties is a key challenge in using chitosan (CS) as a proton exchange membrane (PEM) substrate in direct methanol fuel cells (DMFCs). Herein, a novel nanofiller-zwitterionic molecule, (3-(3-aminopropyl) dimethylammonio) propane-1-sulfonate, ADPS)-modified polydopamine (PDA) (PDA-ADPS) was synthesized by the Michael addition reaction and was incorporated into a CS matrix to prepare CS/PDA-ADPS composite membranes. PDA-ADPS, which contains an acid-based ion pair can create new proton conduction channels in the composite membrane, improving proton conductivity. The proton conductivity of the CS/PDA-ADPS composite membrane was as high as 38.4 mS cm-1 at 80 °C. Moreover, due to the excellent compatibility and dispersibility of PDA-ADPS in the CS matrix, the obtained CS/PDA-ADPS composite membranes exhibited favorable mechanical properties. Such outstanding proton conductivity and mechanical properties guarantee good performance of the composite membranes in fuel cells. The peak power density of the CS/PDA-ADPS composite membranes was 30.2 mW cm-2 at 70 °C. This work provides a new strategy for fabricating high-performance CS based PEMs for DMFCs.

Multifunctional nanoplatform based on tetragonal BaTiO3-Au@polydopamine for computed tomography imaging-guided photothermal synergistic and enhanced piezocatalytic cancer therapy.

Non-centrosymmetric tetragonal barium titanate nanocrystals have the potential to serve as piezoelectric catalysts in cancer therapy. When exposed to ultrasound irradiation, BaTiO3 can generate reactive oxygen species with a noninvasive and deep tissue-penetrating approach. However, the application of BaTiO3 in cancer nanomedicine is limited by their biosafety, biocompatibility, and dosage efficiency. To explore the potential application of BaTiO3 in nanomedical cancer treatment, we introduced ultra-small Au nanoparticles onto the surface of BaTiO3 to enhance the piezoelectric catalytic performance. Additionally, we also coated the BaTiO3 with polydopamine to improve their biosafety and biocompatibility. This led to the preparation of a novel multifunctional BaTiO3-based nanoplatform called BTAPs. In vitro and in vivo experiments demonstrated that the incorporation of Au dopants and polydopamine coating successfully improved the piezoelectric catalysis properties and biocompatibility of BaTiO3. Compared with unmodified BaTiO3, BTAPs achieved a similar piezoelectric catalytic effect at a low dose (0.3 mg ml-1 in vitro and 10 mg kg-1 in vivo). Moreover, BTAPs also exhibited enhanced properties in computed tomography imaging and photothermal effects in vivo. Therefore, BTAPs offer valuable insights into the advantages and limitations of piezoelectric catalytic nanomedicine in cancer treatment.

Hydrolytic nanozymes: Preparation, properties, and applications.

Hydrolytic nanozymes, as promising alternatives to hydrolytic enzymes, can efficiently catalyze the hydrolysis reactions and overcome the operating window limitations of natural enzymes. Moreover, they exhibit several merits such as relatively low cost, easier recovery and reuse, improved operating stability, and adjustable catalytic properties. Consequently, they have found relevance in practical applications such as organic synthesis, chemical weapon degradation, and biosensing. In this review, we highlight recent works addressing the broad topic of the development of hydrolytic nanozymes. We review the preparation, properties, and applications of six types of hydrolytic nanozymes, including AuNP-based nanozymes, polymeric nanozymes, surfactant assemblies, peptide assemblies, metal and metal oxide nanoparticles, and MOFs. Last, we discuss the remaining challenges and future directions. This review will stimulate the development and application of hydrolytic nanozymes.

Protein-coated cobalt oxide-hydroxide nanospheres deliver photosensitizer IR780 iodide for near-infrared light-triggered photodynamic/photothermal/chemodynamic therapy against colon cancer.

Phototherapy has garnered worldwide attention for its minimal invasiveness, controllability, and spatial selectivity in treating cancer. One promising approach involves the use of near-infrared dye IR780, which demonstrates both photodynamic therapy (PDT) and photothermal therapy (PTT) effects under 808 nm laser irradiation. However, this hydrophobic dye's toxicity and limited tumor targeting ability severely hamper its suitability for cancer applications. Herein, a biocompatible nanoplatform CoOOH-IR780@BSA (CoIRB) is developed to efficiently deliver IR780 and provide multi-mode treatments for colon tumors. Due to the nanocarrier coating, CoIRB nanoparticles demonstrated reliable dispersion and stability, and their biotoxicity was substantially reduced for safer blood circulation, which overcame the biological barrier of IR780. The nanoplatform has also shown considerable results in phototherapy in vivo and in vitro experiments, with successful inhibition of MC38 tumor growth through intravenous administration. Additionally, the introduction of cobalt ions could induce Fenton-like reactions to activate the production of toxic hydroxyl radicals (˙OH), exerting an assisted chemodynamic therapy (CDT) effect. Notably, these nanodrugs also exhibited potential as scavengers of reductive glutathione (GSH) and hydrogen sulfide (H2S), leading to amplifying oxidative damage of reactive oxygen species (ROS). Overall, the versatile therapeutic platform, CoIRB, has opened up considerable prospects as a biotherapeutic option for combining PDT/PTT/CDT against colon cancer.

Colloidal Polymer-Templated Formation of Inorganic Nanocrystals and their Emerging Applications.

Inorganic nanocrystals possess unique physicochemical properties compared to their bulk counterparts. Stabilizing agents are commonly used for the preparation of inorganic nanocrystals with controllable properties. Particularly, colloidal polymers have emerged as general and robust templates for in situ formation and confinement of inorganic nanocrystals. In addition to templating and stabilizing inorganic nanocrystals, colloidal polymers can tailor their physicochemical properties such as size, shape, structure, composition, surface chemistry, and so on. By incorporating functional groups into colloidal polymers, desired functions can be integrated with inorganic nanocrystals, advancing their potential applications. Here, recent advances in the colloidal polymer-templated formation of inorganic nanocrystals are reviewed. Seven types of colloidal polymers, including dendrimer, polymer micelle, stare-like block polymer, bottlebrush polymer, spherical polyelectrolyte brush, microgel, and single-chain nanoparticle, have been extensively applied for the synthesis of inorganic nanocrystals. Different strategies for the development of these colloidal polymer-templated inorganic nanocrystals are summarized. Then, their emerging applications in the fields of catalysis, biomedicine, solar cells, sensing, light-emitting diodes, and lithium-ion batteries are highlighted. Last, the remaining issues and future directions are discussed. This review will stimulate the development and application of colloidal polymer-templated inorganic nanocrystals.

Functionalized nanozyme with drug loading for enhanced tumour combination treatment of catalytic therapy and chemotherapy.

Nanozyme-based tumour catalytic therapy has attracted widespread attention in recent years, but the therapeutic efficacy is limited due to the trapping of hydroxyl radicals (˙OH) by endogenous glutathione (GSH) in the tumour microenvironment (TME). Zr/Ce-MOFs/DOX/MnO2 is constructed in this work to serve as a new kind of nanozyme for combination chemotherapy and catalytic treatment. Zr/Ce-MOFs can produce ˙OH in a mimic TME, and the MnO2 on the surface could deplete the GSH, further promoting the ˙OH generation. The pH/GSH dual stimulation accelerates the release of anticancer drug doxorubicin (DOX) in tumour tissue for enhanced tumour chemotherapy. Moreover, Mn2+ produced by the reaction of Zr/Ce-MOFs/DOX/MnO2 and GSH can be used as the contrast agent for T1-MRI. The potential antitumour effect of Zr/Ce-MOFs/DOX/MnO2 is demonstrated by in vitro and in vivo cancer treatment tests. This work thus provides a new nanozyme-based platform for enhanced combination chemotherapy and catalytic treatment for tumours.

Engineering the Hydrophobic Microenvironment in Polystyrene-Supported Artificial Catalytic Triad Nanocatalysts: An Effective Strategy for Improving Catalytic Performance.

Hydrophobic environments have been identified as one of the main parameters affecting the catalytic performance of artificial catalytic triads but are often ignored as an approach to engineering these catalysts. Here, we have developed a simple yet powerful strategy to engineer the hydrophobic environment in polystyrene-supported artificial catalytic triad (PSACT) nanocatalysts. Hydrophobic copolymers containing either oligo(ethylene glycol) side chains or hydrocarbon side chains were synthesized and used for the preparation of nanocatalysts through nanoprecipitation in aqueous media. By using the hydrolysis of 4-nitrophenyl acetate (4NA) as a model reaction, we studied the influence of chemical structures and effective constituent ratios of hydrophobic copolymers on the catalytic performance of PSACT nanocatalysts. Additionally, PSACT nanocatalysts could catalyze the hydrolysis of a few carboxylic esters, even polymers, and be reused for five consecutive runs without significant loss of catalytic activity. This strategy may open an avenue for engineering other artificial enzymes, and these PSACT nanocatalysts have potential applications for the hydrolysis of carboxylic esters.

Wide-Field and Real-Time Super-Resolution Optical Imaging By Titanium Dioxide Nanoparticle-Assembled Solid Immersion Lens.

Super-resolution optical imaging techniques can break the optical diffraction limit, thus providing unique opportunities to visualize the microscopic world at the nanoscale. Although near-field optical microscopy techniques have been proven to achieve significantly improved imaging resolution, most near-field approaches still suffer from a narrow field of view (FOV) or difficulty in obtaining wide-field images in real time, which may limit their widespread and diverse applications. Here, the authors experimentally demonstrate an optical microscope magnification and image enhancement approach by using a submillimeter-sized solid immersion lens (SIL) assembled by densely-packed 15 nm TiO2 nanoparticles through a silicone oil two-step dehydration method. This TiO2 nanoparticle-assembled SIL can achieve both high transparency and high refractive index, as well as sufficient mechanical strength and easy-to-handle size, thus providing a fast, wide-field, real-time, non-destructive, and low-cost solution for improving the quality of optical microscopic observation of a variety of samples, including nanomaterials, cancer cells, and living cells or bacteria under conventional optical microscopes. This study provides an attractive alternative to simplify the fabrication and applications of high-performance SILs.

Recent advances in mixing-induced nanoprecipitation: from creating complex nanostructures to emerging applications beyond biomedicine.

Mixing-induced nanoprecipitation (MINP) is an efficient, controllable, scalable, versatile, and cost-effective technique for the preparation of nanoparticles. In addition to the formulation of drugs, MINP has attracted tremendous interest in other fields. In this review, we highlight recent advances in the preparation of nanoparticles with complex nanostructures via MINP and their emerging applications beyond biomedicine. First, the mechanisms of nanoprecipitation and four mixing approaches for MINP are briefly discussed. Next, three strategies for the preparation of nanoparticles with complex nanostructures including sequential nanoprecipitation, controlling phase separation, and incorporating inorganic nanoparticles, are summarized. Then, emerging applications including the engineering of catalytic nanomaterials, environmentally friendly photovoltaic inks, colloidal surfactants for the preparation of Pickering emulsions, and green templates for the synthesis of nanomaterials, are reviewed. Furthermore, we discuss the structure-function relationships to gain more insight into design principles for the development of functional nanoparticles via MINP. Finally, the remaining issues and future applications are discussed. This review will stimulate the development of nanoparticles with complex nanostructures and their broader applications beyond biomedicine.

A multifunctional nanotheranostic agent based on Lenvatinib for multimodal synergistic hepatocellular carcinoma therapy with remarkably enhanced efficacy.

Lenvatinib (LT), a first-line molecular targeted therapeutic drug for hepatocellular carcinoma (HCC), has been replacing the status of Sorafenib (SF) as the clinically preferred and irreplaceable treatment for a decade. To overcome the low drug utilization and limited single efficacy of LT, ultrasmall copper sulfide nanocrystals (Cu2-xS NCs), and ultrasmall gold nanoparticle (AuNPs) were evenly wrapped into galactosamine conjugated poly(lactide-co-glycolide) (PLGA) as the drug delivery nanoparticles (CAL@PG) by nanoprecipitation. The CAL@PG NPs exhibited excellent stability under physiological conditions, whereas they released LT rapidly in the unique tumor microenvironment (TME) and high temperature, which could be provided by the near-infrared-II (NIR-II) photothermal effect of Cu2-xS NCs. Moreover, the temperature elevation, regenerated hydrogen peroxide (H2O2), and lower pH of TME could substantially boost the reaction potency of copper Fenton-like chemistry. More importantly, this combined therapy significantly improved the efficacy of LT, provided a multifunctional LT delivery system, and enriched the nanoparticle-augmented multimodal synergistic HCC therapy modality.

Protein-supported transition metal catalysts: Preparation, catalytic applications, and prospects.

The immobilization of transition metal catalysts onto supports enables their easier recycling and improves catalytic performance. Protein supports not only support and stabilize transition metal catalysts but also enable the incorporation of biocompatibility and enzymatic catalysis into these catalysts. Consequently, the engineering of protein-supported transition metal catalysts (PTMCs) has emerged as an effective approach to improving their catalytic performance and widening their catalytic applications. Here, we review the recent development of the preparation and applications of PTMCs. The preparation of PTMCs will be summarized and discussed in terms of the types of protein supports, including proteins, protein assemblies, protein-polymer conjugates, and cross-linked proteins. Then, their catalytic applications including organic synthesis, photocatalysis, polymerization, and biomedicine, will be surveyed and compared. Meanwhile, the established catalytic structures-function relationships will be summarized. Lastly, the remaining issues and prospects will be discussed. By surveying a wide range of PTMCs, we believe that this review will attract a broad readership and stimulate the development of PTMCs.

Construction nanoenzymes with elaborately regulated multi-enzymatic activities for photothermal-enhanced catalytic therapy of tumor.

In order to solve the limitation of tumor microenvironment on the anticancer effect of nanozymes, a multifunctional nanoenzyme Co/La-PB@MOF-199/GOx was designed in this work. By doping Co2+ and La3+ in different proportions, Co/La-PB with the optimal photothermal-enhanced catalytic performance was screened, which can catalyze H2O2 to generate more hydroxyl radicals (•OH) and oxygen, showing peroxidase (POD)-like and catalase(CAT)-like property. Through MOF-199 coating and loading glucose oxidase (GOx), a multifunctional nanoenzyme Co/La-PB@MOF-199/GOx was achieved. Due to the pH response of MOF-199, GOx can be accurately released into tumors to catalyze the reaction of glucose and oxygen to produce H2O2. In this process, the oxygen consumption can be compensated by the CAT-like property to realize continuous consumption of glucose and self-supply of H2O2 to continuously produce •OH. In the presence of high oxidation state metal ions (Co3+ and Fe3+), GSH consumption is accelerated to avoid weakening of •OH, showing the glutathione oxidase (GPx-like) activity. Besides, magnetic resonance imaging (MRI) experiments showed the potential application in imaging guided therapy. In vivo anti-tumor experiments showed a satisfactory anti-cancer effect through multi-enzymatic activities.

BSA-coated ß-FeOOH nanoparticles efficiently deliver the photosensitizer chlorin e6 for synergistic anticancer PDT/CDT.

Photodynamic therapy (PDT) has many exceptional advantages in cancer treatment, such as minor trauma, low toxicity side effects, and strong adaptability, effectively overcoming some obstacles of traditional therapy and providing more revolutionary opportunities for curing cancer. Chlorin e6 (Ce6) exhibits excellent singlet oxygen generation and conversion efficiency under near-infrared laser irradiation and is a promising PDT photosensitizer. However, its hydrophobicity, short half-life and lack of tumor specificity limit its in vivo anticancer application. Therefore, this work has designed and prepared a multifunctional nanoplatform, Ce6/FeOOH@BSA, to efficiently deliver Ce6. Nanoparticles exhibit excellent dispersion and stability in deionized water, PBS and DMEM, and the blood half-life is 3.98 ± 0.31 h. The nanoplatform demonstrates effective tumor targeting and accumulation, overcoming the obstacles of the biological application of Ce6. Iron ions can exert a chemodynamic therapy (CDT) effect by reacting with overexpressed H2O2 in the tumor to generate toxic hydroxyl radicals (·OH). Moreover, FeOOH nanoparticles effectively promote glutathione (GSH) consumption in tumor cells, which is conducive to accumulating reactive oxygen species (ROS). In brief, Ce6/FeOOH@BSA nanoparticles realize the targeted delivery of Ce6 and mediate synergistic PDT/CDT against tumors, broadening the biomedical application of nanomaterials.

Core-Shell Microspheres Prepared Using Coaxial Electrostatic Spray for Local Chemotherapy of Solid Tumors.

Local chemotherapy is an alternative therapeutic strategy that involves direct delivery of drugs to the tumor site. This approach avoids adverse reactions caused by the systemic distribution of drugs and enhances the tumor-suppressing effect by concentrating the drugs at the tumor site. Drug-loaded microspheres are injectable sustained-release drug carriers that are highly suitable for local chemotherapy. However, a complex preparation process is one of the main technical difficulties limiting the development of microsphere formulations. In this study, core-shell structured microspheres loaded with paclitaxel (PTX; with a core-shell structure, calcium alginate outer layer, and a poly (lactic acid-co-glycolic acid) copolymer inner layer, denoted as PTX-CA/PLGA-MS) were prepared using coaxial electrostatic spray technology and evaluated in vitro and in vivo. PTX-CA/PLGA-MS exhibited a two-stage drug release profile and enhanced anti-tumor effect in animal tumor models. Importantly, the preparation method reported in this study is simple and reduces the amount of organic solvent(s) used substantially.

Raspberry-like AgBiS2@PVP nanoparticles for enhanced sonodynamic and chemodynamic cancer therapy.

Sonodynamic therapy (SDT) is a non-invasive treatment, preferred by many researchers. Ultrasound is applied to tumor lesions, enriched with a sound sensitizer. The activation of the sound sensitizer produces reactive oxygen species (ROS), which kill the tumor cells. In this study, raspberry-like AgBiS2@PVP nanoparticles (NPs) were prepared, which were modified with polyvinylpyrrolidone (PVP). Finally, AgBiS2@PVP NPs with 261 nm diameter and a suitable band gap were successfully synthesized. These NPs could play a role in SDT by generating ROS when induced by ultrasonic stimulation. Moreover, the AgBiS2@PVP NPs could also catalyze H2O2 in the tumor microenvironment to produce ˙OH, equipping the NPs with chemodynamic therapy (CDT) properties. In vivo and in vitro experiments suggested that, compared to the single treatments, the combination of SDT and CDT had a clearer inhibitory effect on tumor cells.

New anti-cancer explorations based on metal ions.

Due to the urgent demand for more anti-cancer methods, the new applications of metal ions in cancer have attracted increasing attention. Especially the three kinds of the new mode of cell death, including ferroptosis, calcicoptosis, and cuproptosis, are of great concern. Meanwhile, many metal ions have been found to induce cell death through different approaches, such as interfering with osmotic pressure, triggering biocatalysis, activating immune pathways, and generating the prooxidant effect. Therefore, varieties of new strategies based on the above approaches have been studied and applied for anti-cancer applications. Moreover, many contrast agents based on metal ions have gradually become the core components of the bioimaging technologies, such as MRI, CT, and fluorescence imaging, which exhibit guiding significance for cancer diagnosis. Besides, the new nano-theranostic platforms based on metal ions have experimentally shown efficient response to endogenous and exogenous stimuli, which realizes simultaneous cancer therapy and diagnosis through a more controlled nano-system. However, most metal-based agents have still been in the early stages, and controlled clinical trials are necessary to confirm or not the current expectations. This article will focus on these new explorations based on metal ions, hoping to provide some theoretical support for more anti-cancer ideas.

MOF(Fe)-derived composites as a unique nanoplatform for chemo-photodynamic tumor therapy.

Fe-based metal-organic frameworks (MOFs) can be used for chemodynamic therapy (CDT) for tumors due to their unique Fenton-like effects and porous and biodegradable nature. The adsorption and transport of small molecule drugs by their structure has attracted much attention. Herein, MnO2@NH2-MIL101(Fe)@Ce6-F127 nanoparticles (MNMCF NPs) were synthesized using a facile solvothermal strategy. The small molecule photosensitizer Ce6 was adsorbed by MOFs to improve the biocompatibility of Ce6 and give it high bioavailability when injected intravenously. When the MNMCF NPs reached the tumor site, Fe-based MOFs exhibited Fenton-like properties, producing ˙OH and showing CDT effects. MnO2 could specifically respond to produce O2 in a tumor microenvironment, thereby improving the tumor hypoxia state and enhancing the efficacy of photodynamic therapy (PDT) by Ce6. Both the in vitro and in vivo experiments showed that the MNMCF-guided CDT/PDT combination therapy could effectively ablate tumors without the drawbacks of poor tolerability and potential long-term side effects. Therefore, the prepared MNMCF NPs can be used as promising candidates for synergistic CDT/PDT tumor therapy.

Cooperative catalysis of Cu/2,2,6,6-tetramethyl-1-piperidine-N-oxyl nanocatalysts supported by ultraviolet light-responsive polyimides.

The development of ultraviolet (UV) light-regulated cooperative catalysts has attracted wide attention and increased the understanding of structure-activity relationships. Here, we have used azobenzene-containing polyimides as supports for the controllable synthesis of Cu/2,2,6,6-tetramethyl-1-piperidine-N-oxyl (TEMPO) nanocatalysts. Of these nanocatalysts, the catalytic components bearing a pyrene moiety were immobilized onto polyimides containing azobenzene and naphthalene diimide (NDI) moieties via aromatic stacking interactions and hydrophobic interactions in nanoprecipitation. Aromatic stacking clusters were formed and randomly distributed inside nanocatalysts, bringing catalytic components in close proximity for cooperative catalysis. The size of aromatic stacking clusters might be regulated by the UV light-responsive azobenzene units of polyimides. This strategy may find applications in the design and engineering of other multifunctional heterogeneous catalysts with controllable UV light-responsive behaviors.