Immune Complexes Mimicking Synthetic Vaccine Nanoparticles for Enhanced Migration and Cross‐Presentation of Dendritic Cells

The well‐designed activation of dendritic cells (DCs) by enhancing the delivery of antigens and immunostimulatory adjuvants into DCs is a key strategy for efficient cancer immunotherapy. Antigen‐antibody immune complexes (ICs) are known to directly bind to and cross‐link Fc‐gamma receptors (FcγRs) on DCs, which induce enhanced migration of DCs to draining lymph nodes through the up‐regulation of the chemokine receptor CCR7 and cross‐presentation inducing cytotoxic T lymphocyte (CTL) response against tumor antigen. In this study, ICs mimicking synthetic vaccine nanoparticles (NPs) are designed and synthesized by the coating of poly (lactic‐co‐glycolic acid) (PLGA) NPs containing adjuvant (CpG oligodeoxynuleotides (ODNs) as toll‐like receptor 9 ligands) with ovalbumin (OVA) proteins (as model antigens) and by the formation of OVA–OVA antibody ICs. Through the combination of FcγRs‐mediated efficient antigen uptake and CpG ODNs‐based immunostimulation, the secretion of TNF‐α (12.3‐fold), IL‐6 (7.29‐fold), and IL‐12 (11‐fold), homing ability to lymph nodes (7.5‐fold), and cross‐presentation (83.8‐fold IL‐2 secretion) are dramatically increased in DCs treated with PLGA(IC/CpG) NPs. Furthermore, mice vaccinated with DCs treated with PLGA(IC/CpG) NPs induced significant tumor (EG7‐OVA) growth inhibition as well as prolonged survival through CTL‐mediated enhanced cytotoxicity, antigen‐specific responses, and IFN‐γ secretion.     

Biodegradable Dextran Nanogels for RNA Interference: Focusing on Endosomal Escape and Intracellular siRNA Delivery

The successful therapeutic application of small interfering RNA (siRNA) largely relies on the development of safe and effective delivery systems that are able to guide the siRNA therapeutics to the cytoplasm of the target cell. In this report, biodegradable cationic dextran nanogels are engineered by inverse emulsion photopolymerization and their potential as siRNA carriers is evaluated. The nanogels are able to entrap siRNA with a high loading capacity, based on electrostatic interaction. Confocal microscopy and flow cytometry analysis reveal that large amounts of siRNA‐loaded nanogels can be internalized by HuH‐7 human hepatoma cells without significant cytotoxicity. Following their cellular uptake, it is found that the nanogels are mainly trafficked towards the endolysosomes. The influence of two different strategies to enhance endosomal escape on the extent of gene silencing is investigated. It is found that both the application of photochemical internalization (PCI) and the use of an influenza‐derived fusogenic peptide (diINF‐7) can significantly improve the silencing efficiency of siRNA‐loaded nanogels. Furthermore, it is shown that an efficient gene silencing requires the degradation of the nanogels. As the degradation kinetics of the nanogels can easily be tailored, these particles show potential for intracellular controlled release of short interfering RNA.     

Induction of Potent Antitumor Immunity by Sustained Release of Cationic Antigen from a DNA‐Based Hydrogel with Adjuvant Activity

Previous studies indicate that immunostimulatory DNA‐based injectable hydrogels harboring unmethylated cytosine‐phosphate‐guanine (CpG) dinucleotides meet the requirements of an effective antigen delivery system, including safety, biodegradability, ease of administration, and stimulation of the innate immune system. However, rapid release of the model antigen ovalbumin (OVA) from the hydrogel limits its potential. Here, the aim is to achieve sustained OVA release from a DNA hydrogel through cationization of the antigen. Ethylenediamine (ED)‐conjugated cationized OVA (ED‐OVA), but not OVA, forms a complex with hexapod‐like structured DNA, a component of the DNA hydrogel. The release of ED‐OVA from the hydrogel is significantly slower than that of OVA. ED‐OVA mixed with CpG DNA hydrogel efficiently binds to mouse dendritic DC2.4 cells and results in high antigen presentation. Intratumoral injections of ED‐OVA/CpG DNA hydrogel significantly delays tumor growth of OVA‐expressing EG7‐OVA cells in mice. Then, a cationic OVA peptide antigen (R8‐L2‐pepI) consisting of an OVA MHC class I epitope, octaarginine, and a linker is designed. Intratumoral injections of R8‐L2‐pepI/CpG DNA hydrogel eradicate tumors in five out of six mice. Thus, it is concluded that a vaccine consisting of immunostimulatory CpG DNA hydrogel and cationized antigens can be effective for cancer immunotherapy.     

pH/Cathepsin B Hierarchical‐Responsive Nanoconjugates for Enhanced Tumor Penetration and Chemo‐Immunotherapy

An ideal cancer nanomedicine should precisely deliver therapeutics to its intracellular target within tumor cells. However, the multiple biological barriers seriously hinder their delivery efficiency, leading to unsatisfactory therapeutic outcome. Herein, pH/cathepsin B hierarchical‐responsive nanoconjugates (HRNs) are reported to overcome these barriers by sequentially responding to extra‐ and intracellular stimuli in solid tumors for programmed delivery of docetaxel (DTX). The HRNs have stable nanostructures (≈40 nm) in blood circulation for efficient tumor accumulation, while the tumor extracellular acidity induces the rapid dissociation of HRNs into polymer conjugates (≈5 nm), facilitating the deep tumor penetration and cellular internalization. After being trapped into the lysosomes, the conjugates are cleaved by cathepsin B to release bioactive DTX into cytoplasm and inhibit cell proliferation. In addition to the direct inhibition effect, HRNs can trigger the in vivo antitumor immune responses via the immunogenic modulation of tumor cells, activation of dendritic cells (DCs), and generation of cytotoxic T‐cell responses. By employing a combination with α‐PD‐1 (programmed cell death 1) therapy, synergistic antitumor efficacy is achieved in B16 expressing ovalbumin (B16OVA) tumor model. Hence, this strategy demonstrates high efficiency for precise intracellular delivery of chemotherapeutics and provides a potential clinical candidate for cancer chemo‐immunotherapy.     

Zwitterionic Polysulfamide Drug Nanogels with Microwave Augmented Tumor Accumulation and On‐Demand Drug Release for Enhanced Cancer Therapy

Zwitterionic polymers demonstrate as a class of antifouling materials with long blood circulation in living subjects. Despite extensive research on their antifouling abilities, the responsive zwitterionic polymers that can change their properties by mild outside signals are poorly explored. Herein, a sulfamide‐based zwitterionic monomer is developed and used to synthesize a series of polysulfamide‐based (poly (2‐((2‐(methacryloyloxy)ethyl) dimethylammonio)acetyl) (phenylsulfonyl) amide (PMEDAPA)) nanogels as drug carriers for effective cancer therapy. PMEDAPA nanogels are proved to exhibit prolonged blood circulation without inducing the accelerated blood clearance phenomenon. Intriguingly, PMEDAPA nanogels can sensitively respond to hyperthermia by adjusting the crosslinker degree. After modified with transferrin (Tf), the nanogels (PMEDAPA‐Tf) achieve shielded tumor targeting at normothermia, while exhibiting recovered tumor targeting at hyperthermia, leading to enhanced tumor accumulation. Meanwhile, PMEDAPA‐Tf nanogels show superior penetration ability in 3D tumor spheroids and faster drug release at hyperthermia compared with that at normothermia. In combination with mild microwave heating (≈41 °C), the drug‐loaded PMEDAPA‐Tf nanogels show a pronounced tumor inhibition effect in a humanized orthotropic liver cancer model. Therefore, the study provides a novel hyperthermia‐responsive zwitterionic nanogel that can achieve augmented tumor accumulation and on‐demand drug release assisted with clinically used microwave heating for cancer therapy.     

Biocompatible PEG‐Chitosan@Carbon Dots Hybrid Nanogels for Two‐Photon Fluorescence Imaging,Near‐Infrared Light/pH Dual‐Responsive Drug Carrier,and Synergistic Therapy

This work designs a class of biocompatible PEG‐chitosan@CDs hybrid nanogels by integrating nonlinear poly(ethylene glycol) (PEG), chitosan, and graphitic carbon dots (CDs) into a single nanoparticle for two‐photon fluorescence (TPF) bioimaging, pH and near‐infrared (NIR) light dual‐responsive drug release, and synergistic therapy. Such hybrid nanogels can be simply prepared from a one‐pot surfactant‐free precipitation polymerization of the PEG macromonomers complexed with chitosan and CDs in water, resulting in a semi‐interpenetration of chitosan chains and an immobilization of CDs in the nonlinear PEG networks. The embedded CDs in hybrid nanogels not only serve as an excellent confocal and TPF imaging contrast agent and fluorescent pH‐sensing probe, but also enhance the loading capacity of the hybrid nanogels for hydrophobic anticancer drug. The chitosan can induce a pH‐sensitive swelling/deswelling of the hybrid nanogels for pH‐regulated drug release over the physiologically important range of 5.0–7.4 and surface modulation of embedded CDs to realize fluorescent pH sensing. The thermosensitive nonlinear PEG network can promote the drug release through the local heat produced by the embedded CDs under NIR irradiation. The in vitro results indicate that the hybrid nanogels demonstrated high therapeutic efficacy through the synergistic effect of combined chemo–photothermal treatments.     

Engineering a Nanoscale Al‐MOF‐Armored Antigen Carried by a “Trojan Horse”‐Like Platform for Oral Vaccination to Induce Potent and Long‐Lasting Immunity

Vaccination via the oral administration of an antigen faces many challenges, including gastrointestinal (GI) proteolysis and mucosal barriers. To limit GI proteolysis, a biomimetically mineralized aluminum‐based metal–organic framework (Al‐MOF) system that is resistant to ambient temperature and pH and can act synergistically as a delivery vehicle and an adjuvant is synthesized over a model antigen ovalbumin (OVA) to act as armor. To overcome mucosal barriers, a yeast‐derived capsule is used to carry the Al‐MOF‐armored OVA as a “Trojan Horse”‐like transport platform. In vitro experiments reveal that the mineralization of Al‐MOFs forms an armor on OVA that protects against highly acidic and degradative GI conditions. However, the mineralized Al‐MOFs can gradually disintegrate in a phosphate ion‐containing simulated intracellular fluid, slowly releasing their encapsulated OVA. In vivo studies reveal that the “Trojan Horse”‐like transport platform specifically targets intestinal M cells, favoring the transepithelial transport of the Al‐MOF‐armored OVA, followed by subsequent endocytosis in local macrophages, ultimately accumulating in mesenteric lymph nodes, yielding long‐lasting, high‐levels of mucosal S‐IgA and serum IgG antibodies. Such an engineered delivery platform may represent a promising strategy for the oral administration of prophylactic or therapeutic antigens for vaccination.     

Disulfide‐Bridged Organosilica Frameworks: Designed,Synthesis, Redox‐Triggered Biodegradation,and Nanobiomedical Applications

Over the past few years, silica‐based nanotheranostics have demonstrated their great potential for nano/biomedical applications. However, the uncontrollable and difficult degradability of their pure silica framework and long‐time in vivo retention still cause severe and unpredictable toxicity risks. Therefore, it is highly desirable to design and synthesize materials with safer framework structures and compositions. To this aim, the introduction of disulfide bonds into the silica framework can not only maintain high stability in physiological conditions, but also achieve a stimuli‐responsive biodegradation triggered by intracellular reducing microenvironment in living cells, especially in cancer cells. Once nanotheranostics with disulfide (i.e., thioether)‐bridged silsesquioxane framework are taken up by tumor cells via passive or active targeting, the disulfide bonds in the hybrid silica matrix can be cleaved by a high concentration of intracellular glutathione, enabling redox‐triggered biodegradation of the nanosystems for both concomitant release of the loaded therapeutic cargo and in vivo clearance. It is envisioned that such hybrid materials comprised of disulfide‐bridged silsesquioxane frameworks can become promising responsive and biodegradable nanotheranostics. This review summarizes the recent advances in the synthesis of hybrid organosilicas with disulfide‐bridged silsesquioxane frameworks, and discuss their redox‐triggered biodegradation behaviors combined with their biocompatibility and nanobiomedical applications.     

Off‐Stoichiometric Thiol‐Ene Chemistry to Dendritic Nanogel Therapeutics

A novel platform of dendritic nanogels is herein presented, capitalizing on the self‐assembly of allyl‐functional polyesters based on dendritic‐linear‐dendritic amphiphiles followed by simple cross‐linking with complementary monomeric thiols via UV initiated off‐stoichiometric thiol‐ene chemistry. The facile approach enabled multigram creation of allyl reactive nanogel precursors, in the size range of 190–295 nm, being readily available for further modifications to display a number of core functionalities while maintaining the size distribution and characteristics of the master batch. The nanogels are evaluated as carriers of a spread of chemotherapeutics by customizing the core to accommodate each individual cargo. The resulting nanogels are biocompatible, displaying diffusion controlled release of cargo, maintained therapeutic efficacy, and decreased cargo toxic side effects. Finally, the nanogels are found to successfully deliver pharmaceuticals into a 3D pancreatic spheroids tumor model.     

Smart Supramolecular “Trojan Horse”‐Inspired Nanogels for Realizing Light‐Triggered Nuclear Drug Influx in Drug‐Resistant Cancer Cells

Efficient nuclear delivery of anticancer drugs evading drug efflux transporters (DETs) on the plasma and nuclear membranes of multidrug‐resistant cancer cells is highly challenging. Here, smart nanogels are designed via a one‐step self‐assembly of three functional components including a biocompatible copolymer, a fluorescent organosilica nanodot, and a photodegradable near‐infrared (NIR) dye indocyanine green (ICG). The rationally designed nanogels have high drug encapsulation efficiency (≈99%) for anticancer drug doxorubicin (Dox), self‐traceability for bioimaging, proper size for passive tumor targeting, prolonged blood circulation time for enhanced drug accumulation in tumor, and photocontrolled disassemblability. Moreover, the Dox‐loaded nanogels can effectively kill multidrug‐resistant cells via two steps: 1) They behave like a “Trojan horse” to escape from the DETs on the plasma membrane for efficiently transporting the anticancer “soldier” (Dox) into the cytoplasm and preventing the drugs from being excreted from the cells; 2) Upon NIR light irradiation, the photodegradation of ICG leads to the disassembly of the nanogels to release massive Dox molecules, which can evade the DETs on the nuclear membrane to exert their intranuclear efficacy in multidrug‐resistant cells. Combined with their excellent biocompatibility, the nanogels may provide an alternative solution for overcoming cancer multidrug resistance.     

Robust Nanovaccine Based on Polydopamine-Coated Mesoporous Silica Nanoparticles for Effective Photothermal-Immunotherapy Against Melanoma

Nanoparticle-based combination therapy strategy of photothermal therapy (PTT) and immunotherapy is an attractive cancer treatment for ablating tumors and eliciting host immune responses. However, this strategy is often hampered by tedious treatment process and limited immune response, and usually needs to be combined with checkpoint blockades to enhance therapeutic effect. Herein, a nanoplatform with mesoporous silica nanoparticles (MSNs) as a vector, which integrated photothermal agent polydopamine (PDA), model antigen ovalbumin (OVA), and antigen release promoter ammonium bicarbonate (ABC) in an easy way for melanoma PTT-immunotherapy is designed. The formulated MSNs-ABC@PDA-OVA nanovaccine exhibits excellent photothermal properties and effectively eliminates primary tumors. Under laser irradiation, the MSNs-ABC@PDA-OVA nanovaccine realizes rapid antigen release and endosome escape, enhances dendritic cells activation and maturation, facilitates migration to tumor-draining lymph nodes, and induces robust antitumor immune responses. Impressively, single injection of MSNs-ABC@PDA-OVA combines with single round of PTT successfully eradicates melanoma tumors with a cure rate of 75% and generates strong immunological memory to inhibit tumor recurrence and lung metastasis. Hence, the research offers a simple and promising strategy of synergistic PTT-immunotherapy to effectively treat cancer.     

Rigid Shell Decorated Nanodevice with Fe/H2O2 Supply and Glutathione Depletion Capabilities for Potentiated Ferroptosis and Synergized Immunotherapy

The overexpressed glutathione peroxidase4 (GPX4) and insufficient H₂O₂ in tumor cells weaken ferroptosis therapy and the elicited anticancer immune response. Herein, a rigid metal-polyphenol shell decorated nanodevice ssPPE_Lap@Fe-TA is constructed to successfully overcome the drawbacks of ferroptosis therapy. The ssPPE_Lap@Fe-TA consists of a rigid Fe-TA network-based shell and disulfide-containing polyphosphoester (ssPPE) core with β-lapachone loading. The rigid Fe-TA network-based shell of ssPPE_Lap@Fe-TA enables its efficient internalization by tumor cell and then disintegrates in the acidic endosome/lysosome to initiate Fe³⁺/Fe²⁺ conversion-driven ferroptosis. The ssPPE core will deplete glutathione (GSH) via the disulfide-thiol exchange reaction to inactivate GPX4, and also trigger the release of β-lapachone to significantly increase intracellular H₂O₂ and then promote Fe³⁺-mediated Fenton reaction, eventually achieving strong inhibition of tumor progression. Moreover, ssPPE_Lap@Fe-TA elicites a robust systemic antitumor immune response by promoting dendritic cells (DCs) maturation and T cell infiltration, and synergizes with anti-PD-L1 antibody (a-PD-L1) to strikingly suppress 4T1 tumor growth and lung metastasis.     

Design of Multiresponsive Hydrogel Particles and Assemblies

In the realm of soft nanotechnology, hydrogel micro‐ and nanoparticles represent a versatile class of responsive materials. Over the last decade, our group has investigated the synthesis and physicochemical properties of a variety of synthetic hydrogel particles. From these efforts, several particle types have emerged with potentially enabling features for biological applications, including nanogels for targeted drug delivery, microlenses for biosensing, and coatings for biomedical devices. For example, core/shell nanogels have been used to encapsulate and deliver small interfering RNA to ovarian cancer cells; nanogels used in this fashion may improve therapeutic outcomes for a variety of macromolecular therapeutics. Microgels arranged as multilayers on implantable biomaterials greatly minimize the host inflammatory response to the material. Furthermore, the triggered release of drugs (i.e., insulin) has been demonstrated from similar assemblies. The goal of this feature article is to highlight developments in the design of responsive microgels and nanogels in the context of our recent efforts and in relation to the community that has grown up around this fascinating class of materials.     

Enzyme‐Catalyzed Formation of Supramolecular Hydrogels as Promising Vaccine Adjuvants

Promising vaccine adjuvants of self‐assembling peptide hydrogels for protein ovalbumin (OVA) are introduced in this study. The hydrogels are formed by the enzyme of phosphatase, and the vaccine adjuvant potency of both l ‐ and d ‐peptide hydrogels is evaluated. The results indicate that, compared with the clinically used alum adjuvant, both l ‐ and d ‐peptide hydrogels can increase the IgG production of OVA for about 1.3 and 3.8 times, respectively. Both gels can enhance antigen uptake and induce dendritic cell maturation, and promote and prolong accumulation of antigen in lymph node, as well as evoke germinal center formation. However, the d ‐peptide hydrogel with OVA exhibits a slightly more efficient accumulation of OVA in the lymph nodes and seems preventing tumor growth more significantly than its l ‐counterpart. With the good biocompatibility and degradability of peptide hydrogels, the hydrogels described in this study have big potential for the production of protein vaccines for immunotherapy against different diseases.     

Synthesis,Reductive Cleavage,and Cellular Interaction Studies of Biodegradable,Polyglycerol Nanogels

In this paper we describe disulfide containing, polyglycerol nanogels as a new class of biodegradable materials. These nanoparticles are prepared in inverse miniemulsion via an acid catalyzed ring‐opening polyaddition of disulfide containing polyols and polyepoxides. Varying conditions allow us to tune particle size and disulfide content within the polymer network; particles can be prepared with narrow polydispersities and diameters in the range from 25 to 350 nm. Particle degradation under reductive intracellular conditions is studied by various analytical techniques. Gel permeation chromatography indicates that final degradation products have relatively low molecular weights (≤ 5 kDa). In addition, studies in cell culture show these nanoscale materials to be highly biocompatible. Dye‐labelled nanogels are shown by optical microscopy techniques to readily internalize into cells by endocytotic mechanisms. This study highlights the great potential of these particles to function as sophisticated nanotransporters that deliver cargo to a certain tissue or cell target and then biodegrade into smaller fragments which would be cleared from the body by the kidney. (with ≈ 30 kDa molecular weight cut off)     

Amphiphilic Poly(Amino Acid) Nanoparticles Induce Size‐Dependent Dendritic Cell Maturation

Size‐regulated amphiphilic poly(amino acid) nanoparticles (NPs) composed of poly(γ‐glutamic acid) (γ‐PGA) and the hydrophobic amino acid derivative, L ‐phenylalanine ethyl ester (Phe) are prepared to evaluate the effects of particle size on dendritic cell (DC) uptake of NPs and their immune stimulatory activities as delivery carriers and adjuvants. The size of the Phe‐conjugated γ‐PGA NPs (γ‐PGA–Phe NPs) is easily controlled by regulating the aggregated γ‐PGA–Phe numbers. Each of the differently sized γ‐PGA–Phe NPs could efficiently encapsulate ovalbumin (OVA), and the amount of encapsulated OVA per milligram of NPs is almost the same despite the differences in size. The DC uptake of small NPs is lower than for the larger NPs, but the effect of DC activation by NPs is high in the small sizes. The DC activation is significantly affected by the size of the NPs, which suggests that not only the uptake process of the NPs, but also the surface interactions between the NPs and DCs, is important for the induction of DC maturation. The precisely size‐controllable γ‐PGA–Phe NPs have significant potential as an antigen carrier and vaccine adjuvant. These results should provide guidelines for adjuvant design in the development of an effective vaccine.     

Cationic Lipids-Mediated Dual-Targeting of Both Dendritic Cells and Tumor Cells for Potent Cancer Immunotherapy

Impaired antigen presentation either in dendritic cells (DCs) or tumor cells impedes the triggering of antitumor immunity or tumor cell killing, resulting in failures of multiple types of cancer immunotherapy. Herein, the strategy of using dual-targeting nanomedicines to simultaneously improve the presentation of tumor antigens by both DCs and tumor cells is proposed. It is shown that tuning of surface charge of nanoparticles (NPs) by incorporating different amounts of cationic lipids alters the in vivo NP tissue accumulation and cellular targeting profiles. NPs with moderately positive surface charge (≈20 mV) achieve efficient accumulation in tumors and lymph nodes and dual-targeting to both DCs and tumor cells. As a proof-of-concept demonstration, siRNA against YTH N6−methyladenosine RNA binding protein 1 (YTHDF1) is delivered by the dual-targeting NPs to inhibit excessive antigen degradation in both DCs and tumor cells. For DCs, YTHDF1 downregulation promotes tumor antigen cross-presentation and cross-priming of antigen-specific T cells. For tumor cells, it enhances the presentation of endogenous tumor antigens and hence improves both the recognition and killing of tumor cells by primed antigen-specific T cells. The dual-targeting nanomedicines generate efficient antitumor immunity.     

Stabilization of Glucagon by Trehalose Glycopolymer Nanogels

Glucagon is a peptide hormone used for the treatment of hypoglycemia; however, its clinical potential is limited by its insolubility and instability in solution. Herein, the encapsulation, stabilization, and release of glucagon by trehalose glycopolymer nanogels are reported. Methacrylate‐functionalized trehalose is copolymerized with pyridyl disulfide ethyl methacrylate using free radical polymerization conditions to form trehalose glycopolymers with thiol‐reactive handles. Glucagon is chemically modified to contain two thiol groups and is subsequently utilized as the cross‐linker to form redox‐responsive trehalose nanogels with greater than 80% conjugation yield. Nanogel formation and subsequent glucagon stabilization are characterized using polyacrylamide gel electrophoresis, dynamic light scattering, and transmission electron microscopy. It is determined that the solution stability of the glucagon increased from less than 24 h to at least three weeks in the nanogel form. Additionally, in vitro activity of the synthesized glucagon analog and released glucagon is investigated, demonstrating that the glucagon remains active after modification. It is anticipated that these glucagon–nanogel conjugates will be useful as a stabilizing glucagon formulation, allowing for cargo release under mild reducing conditions.     

Metal–Organic Framework Assisted and Tumor Microenvironment Modulated Synergistic Image‐Guided Photo‐Chemo Therapy

The complex tumor microenvironment (TME) and nonspecific drug targeting limit the clinical efficacy of photodynamic therapy in combination with chemotherapy. Herein, a metal–organic framework (MOF) assisted strategy is reported that modulates TME by reducing tumor hypoxia and intracellular glutathione (GSH) and offers targeted delivery and controlled release of the trapped chemodrug. Platinum(IV)‐diazido complex (Pt(IV)) is loaded inside a Cu(II) carboxylate‐based MOF, MOF‐199, and an aggregation‐induced‐emission photosensitizer, TBD, is conjugated to polyethylene glycol for encapsulating Pt(IV)‐loaded MOF‐199. Once the fabricated TBD‐Pt(IV)@MOF‐199 nanoparticles are internalized by cancer cells, MOF‐199 consumes intracellular GSH and decomposes to fragments to release Pt(IV). Upon light irradiation, the released Pt(IV) generates O₂ that relieves hypoxia and produces Pt(II)‐based chemodrug inside cancer cells. Concomitantly, efficient reactive oxygen species generation and bright emission are afforded by TBD, resulting in synergistic image‐guided photo‐chemo therapy with enhanced efficacies and mitigated side effects.     

One Stone,Two Birds: Spidroin-Inspired Nanogels for High-Performance Fibers and Photothermal Actuators

The exciting development of hydrogels makes it a promising candidate to be applied in various fields. However, it remains a great challenge to store the precursors of hydrogels and to process them after gelation, like synthetic polymer materials. Herein, spidroin-inspired novel nanogels with extraordinary processability, which can be spun into fibers via direct drawing and fabricated into thermal actuators easily after gelation are prepared. These soluble and spinnable nanogels are composed of a liquid metal core and a poly (acrylic acid) (PAA) shell and are entangled with each other. The as fabricated nanogels and diluted dope solution can be stored >1 month. The as-spun nanogel fibers with hierarchical structures achiev extraordinary mechanical properties (tensile stress of 575 MPa, toughness of 381 MJ m⁻³) and supercontraction at 60% RH. Besides, a photothermal actuator is prepared by coating the nanogels on a polyethylene substrate with a commercial shading ink, and the as-prepared actuator shows a rapid response to near-infrared light as well as a fast recovery. Molecular dynamics simulation reveals a possible working mechanism of the actuator. This study provides a new strategy to prepare processable nanogels with broad application prospects for smart textiles and soft robots.