Aug 2026· Biomaterials· Vol 337, pp.
124540
· 0 citations· 47 references
Medicine
TL;DR
In mouse, rabbit, and non-human primate models with MPXV-induced skin damage, this hydrogel nanoparticle protective layer significantly inhibits viral replication and accelerates wound healing, representing a transformative, convertible platform for treating MPXV and other highly inflammatory viral infections.
Abstract
Currently, monkeypox virus (MPXV) treatment methods face a dilemma of potential drug resistance. They cannot simultaneously address two core pathological mechanisms driving infection: continuous viral replication and uncontrolled inflammatory storm. To overcome these challenges, we innovatively developed a dual-function therapeutic strategy with precise virus clearance and anti-inflammatory effects, constructing a dual hydrogel system synergistically combining phototherapy and immunomodulatory effects. Specifically, aggregation-induced emission (AIE) nanoparticles (NPs) are embedded in a reactive oxygen species (ROS)-degradable polyvinyl alcohol (PVA)-N1-(4-borobenzoyl)-N3-(4-borobenzoyl)-the N1, the N1, N3, N3-tetramethylpropane-1,3-diamine (tsPBA) hydrogel, while the anti-inflammatory agent is loaded in a zwitterionic hydrogel (SBMA) matrix. Under near-infrared band laser irradiation, AIE NPs efficiently generate large amounts of ROS, which, together with inflammation-produced endogenous ROS, trigger the rapid degradation of the ROS-responsive hydrogel and release of AIE NPs. The generated ROS effectively destroys the MPXV shell and strongly inactivates the virus. After virus clearance, the SBMA hydrogel continuously releases anti-inflammatory drugs (Dexamethasone, DXMS) to inhibit excessive pro-inflammatory cytokines and reduce inflammation-induced tissue damage. In mouse, rabbit, and non-human primate models with MPXV-induced skin damage, this hydrogel nanoparticle protective layer significantly inhibits viral replication and accelerates wound healing, representing a transformative, convertible platform for treating MPXV and other highly inflammatory viral infections.
A visible-light-responsive organic nanoplatform (iTPyPXs/SCM) that improves ROS utilization for antimicrobial therapy while limiting excessive intracellular ROS and provides a safer and more effective biomaterial strategy for photodynamic therapy in infected wound healing is developed.
Hongyu Lin, Qingyang Peng, Ying Lin et al.· Biomaterials· 0 citations
Photodynamic therapy (PDT) holds promise for combination antitumor therapies by triggering immunogenic cell death (ICD). ICD is defined as the process by which tumor cells, upon death induced by external stimuli, convert from a non‑immunogenic to an immunogenic state, thereby mediating an anti‑tumor immune response in the host. But the poor aqueous solubility and inadequate tumor targeting of photosensitizers hinder their clinical translation. This study focuses on a novel BODIPY photosensitizer (M5) and aims to improve its antitumor efficacy via efficient tumor-targeted delivery and controllable release. Herein, we successfully synthesized iRGD-functionalized DSPE-PEG2000-iRGD and pH-sensitive HA-g-DEAP polymers, and further fabricated multifunctional M5/NMN/DEAP/iRGD-Lip liposomes via the thin-film dispersion method, which possess pH responsiveness and enhanced tumor-targeting ability. β-Nicotinamide Mononucleotide (NMN), a NAD + precursor, exerts a potent stimulatory effect on T-cell activation; 3-(Diethylamino)propylamine (DEAP) and hyaluronic acid (HA) can form pH-responsive HA-g-DEAP; the iRGD peptide (CRGDK/RGPDC), upon hydrolysis at its C‑terminus, exposes a motif that binds to neuropilin‑1 (NRP1), thereby conferring tumor‑targeting and tissue‑penetrating properties, endowing the liposomes with tumor-targeting and tissue-penetrating capabilities. M5 exhibits a high molar absorption coefficient of 5.33 × 104 M⁻¹ cm⁻¹ and a singlet oxygen quantum yield of 0.3854. In vitro cellular assays showed IC50 values of 104.1 nM and 72.68 nM in breast cancer MDA-MB-231 and 4T1 cells, respectively. Treatment with M5/NMN/DEAP/iRGD-Lip induced apoptosis rates of 56.84% and 55.6% in MDA-MB-231 and 4T1 cells, respectively. T-cell co-culture assays showed that M5/NMN/DEAP/iRGD-Lip increased the proportions of CD4+ and CD8+ T cells while reducing the proportion of regulatory T cells (Tregs) among CD4+ T cells. Collectively, the multifunctional M5/NMN/DEAP/iRGD-Lip liposomes integrate targeted delivery, pH-controlled release, and synergistic PDT-immunotherapy, effectively addressing key limitations of conventional photosensitizers. This work provides a promising nanoplatform for the development of novel combination therapies against breast cancer, laying a foundation for future preclinical and clinical translations.
Junwei Zhuang, Chen Guo, Xingming Ye et al.· Colloids and Surfaces B: Bio...· 0 citations
Osteosarcoma (OS) is characterized by a profoundly immunosuppressive tumor microenvironment (TME) that limits the efficacy of immunotherapy. Although photothermal therapy (PTT) can induce immunogenic cell death (ICD) and promote tumor antigen release, it is insufficient to elicit durable antitumor immunity. Here, we develop a tumor microenvironment-responsive injectable hydrogel (MP@TPH) that mechanistically integrates photothermal ablation with localized activation of innate immunity. MP@TPH co-encapsulates polydopamine nanoparticles and PDA-coated MSA-2, a stimulator of interferon genes (STING) agonist, enabling near-infrared-induced tumor ablation and reactive oxygen species (ROS)-triggered release of immune modulators. Mechanistically, PTT-induced ICD facilitates antigen liberation, while ROS-responsive delivery of MSA-2 enhances dendritic cell activation and immune priming. In a murine K7M2 osteosarcoma model, MP@TPH combined with irradiation markedly suppresses tumor growth without detectable systemic toxicity. This work establishes a TME-adaptive platform that couples photothermal therapy with spatially confined STING activation, offering a mechanistically grounded strategy to overcome immune resistance in osteosarcoma.
Zhaolong Yu, Qiuqun Xiao, Zhongyi Sun et al.· Photodiagnosis and Photodyna...· 0 citations
Photothermal therapy can induce local tumor cell death and trigger antitumor immune responses. However, its efficacy is often limited by insufficient lymph node immune priming and by sustained ROS generated from thermal stress, which suppress immune cell function. An oxidative-stress-responsive injectable hydrogel-nanoparticle composite (TP@PPM) was constructed by embedding MSA-2-loaded PEGylated polydopamine nanoparticles (PPM) into a TSPBA-PVA hydrogel. Upon near-infrared (NIR) irradiation, PPM mediated photothermal cytotoxicity, induced tumor-cell thermal stress and mitochondrial dysfunction, and generated reactive oxygen species (ROS), triggering immunogenic cell death. The relatively stable and diffusible H2O2 generated within the tumor microenvironment can enter the tumor interstitium and oxidize boronate ester crosslinks in the hydrogel, thereby promoting hydrogel degradation and enabling controlled PPM release. Then, the PPM accumulated in tumor-draining lymph nodes within 6 h and delivered MSA-2 to dendritic cells and activated the STING pathway. In vitro, TP@PPM attenuated MDSC-associated ROS accumulation and restored T cell proliferation to 44.8% in an MDSC-T cell coculture system. In vivo, TP@PPM combined with NIR irradiation promoted the infiltration of CD8+/CD4+ T cell and reduced pulmonary metastasis of the tumor. This hydrogel-nanoparticle composite platform helps overcome photothermal therapy-induced immune suppression, reduce oxidative stress in the TME, and inhibit tumor metastasis, offering a promising strategy for enhancing cancer immunotherapy.
Jie Sun, Yunyun Wu, Sheng Zhao et al.· ACS Applied Materials and In...· 0 citations
Nasopharyngeal carcinoma (NPC) therapy faces challenges including severe off-target toxicity and immunosuppression. Here, a biomimetic nanogel vaccine is developed based on dual pH/reactive oxygen species (ROS)-responsive poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) that were co-loaded with indocyanine green (ICG) and the endoplasmic reticulum stress-inducing drug toyocamycin, followed by coating with cancer cell membranes (CMs) or exosomes (Exos). Systematic comparison reveals that CM coating confers better homologous targeting, cellular uptake, and immunogenicity than the Exo coating. The optimized IT@PVCL-CM NGs enable tumor microenvironment-triggered drug release, combined chemotherapy and mild photothermal therapy, and synergistic induction of immunogenic cell death (ICD). In an NPC mouse model, the IT@PVCL-CM combined with laser irradiation significantly promotes dendritic cell maturation through the combination therapy-mediated ICD effect and the CM antigens, CD8+ T cell infiltration, and long-term memory T cell responses, effectively suppressing both primary and distant tumors via an abscopal effect. Additionally, ICG endows dual-modal fluorescence and thermal imaging for real-time tumor monitoring. This work presents the integration of dual-responsive PVCL nanogels, dual ICD induction strategies through combination of photothermo-chemotherapy, and biomimetic membrane cloaking for precision NPC theranostics and immune activation.
Shanbin Wen, Yifan Huang, Xianghao Xiao et al.· ACS Applied Materials and In...· 0 citations
Osteoarthritis (OA) is characterized by sterile intra-articular inflammation and progressive cartilage degeneration. Nanoparticle-based photothermal therapy (PTT) offers a promising intervention for OA therapy; however, drug-release control under photothermal conditions remains underexplored. Here, we present a Prussian blue-based, near-infrared (NIR) -responsive hydrogel (GPT) that enables multi-target therapy for OA through co-encapsulation of Prussian blue nanoparticles (PBNPs) and tannic acid (TA) within a thermosensitive agarose matrix. TA coordinates with unsaturated iron sites on PBNPs, synergistically enhancing antioxidant capacity while maintaining robust photothermal performance. Harnessing the thermal phase transition of low-melting-point agarose, GPT enables precise, temperature-dependent drug release: NIR irradiation triggers accelerated release within a mild therapeutic window, whereas drug release slowly in the absence of stimulation. Co-released TA/PBNPs rapidly scavenge excessive reactive oxygen species (ROS), delay chondrocyte senescence, and restore metabolic homeostasis. Moreover, the localized hyperthermia activates HSP70, enhancing chondroprotection under inflammatory stress. In mice model of OA, GPT/NIR treatment effectively slows disease progression. Transcriptomic profiling further reveals suppression of IL-17 signaling as a key mechanism contributing to reduced cartilage degradation. This platform synergistically combines controlled drug delivery and PTT, achieving unprecedented integration of IL-17 pathway inhibition with a photothermal-antioxidant system for OA treatment. It enables concurrent metabolic reprogramming and structural preservation, offering a novel strategy for disease-modifying OA therapy.
Xiaoyang Chen, Yao Li, Zilong Wang et al.· Colloids and Surfaces B: Bio...· 0 citations