Electrostatically assembled gold nanocluster-enhanced porphyrinic metal-organic framework nanozymes for oxygen-boosted photodynamic therapy of hypoxic tumors.

Porphyrin-copper (II) covalent organic framework nanoplatform with intrinsic bifunctional photodynamic and chemodynamic activities for synergistic multimodal cancer therapy

Photodynamic therapy (PDT) efficacy is severely compromised by tumor hypoxia and the scarcity of efficient type-I photosensitizers, necessitating multimodal therapeutic strategies. Herein, we report a porphyrin-Cu (II) covalent organic framework (TBCOF) with intrinsic bifunctional photodynamic and chemodynamic activities. Sequential DOX encapsulation and hyaluronic acid (HA) surface functionalization afford HA-TBCOF@DOX, a tumor-targeted nanoplatform integrating four synergistic therapeutic modalities. Under 660 nm laser irradiation, the nanoplatform generates ROS signatures consistent with both type-I and type-II pathways for PDT, while the intrinsic Cu2+ centers are proposed to catalyze a Fenton-like reaction consistent with •OH generation for CDT. Concurrently, observations of O2 evolution suggest catalase-like activity that may decompose endogenous H2O2 into O2, alleviating hypoxia and potentiating oxygen-dependent PDT. Efficient photothermal conversion and pH-triggered DOX release contribute to photothermal and chemotherapeutic effects, respectively, while HA-mediated CD44 targeting enhances cellular uptake and therapeutic specificity. In vitro and in vivo studies demonstrate that laser-activated HA-TBCOF@DOX effectively suppresses tumor growth, induces apoptosis, and exhibits no apparent systemic toxicity under the tested experimental conditions. This work establishes a multifunctional COF-based nanoplatform that addresses PDT limitations observed in this study by integrating intrinsic PDT and CDT, providing a robust strategy for synergistic multimodal cancer therapy.

Metal-organic cage-mediated synergistic tumor microenvironment remodeling and self-enhanced photodynamic therapy.

Cerium molybdate-doped polyaniline nanoplatform for GSH-depletion-enhanced chemodynamic/NIR-II photothermal synergistic therapy via ferroptosis and immune activation

Cerium molybdate-doped polyaniline nanoparticles are developed to enable a synergistic combination of photothermal therapy (PTT) and CDT, thereby triggering immunogenic cell death (ICD) and enhancing antitumor immunity and presenting a robust nanoplatform integrating chemodynamic and photothermal therapies for potent cancer immunotherapy.

Cold Atmospheric Plasma Potentiates the Photodynamic Effects of Protoporphyrin IX-Loaded Mesoporous Silica-Coated Iron Oxide Nanoclusters in HaCaT Cells

Photodynamic therapy (PDT) is a reactive oxygen species (ROS)-based treatment modality whose efficacy is often limited by poor photosensitizer stability and delivery. In this study, mesoporous silica-coated iron oxide nanoclusters (MNCs) were synthesized and loaded with protoporphyrin IX (PPIX) to obtain a multifunctional PPIX@MNC nanoplatform. Physicochemical characterization was performed using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, and Fourier-transform infrared spectroscopy (FTIR). The biological effects of MNC, free PPIX, and PPIX@MNC were evaluated in HaCaT cells—as a general epithelial model—under dark conditions, light irradiation, cold atmospheric plasma (CAP) exposure, and combined CAP-assisted photodynamic treatment. FTIR, DLS, and zeta potential analyses confirmed successful incorporation of PPIX into the nanoclusters. Cell viability assays revealed pronounced phototoxicity of free PPIX, with the IC50 value decreasing from 44.4 ± 3.5 nM under dark conditions to 14 ± 2 nM following light activation, corresponding to a phototoxicity index of 3.17. CAP further enhanced PPIX-mediated cytotoxicity, and the CAP-assisted photodynamic group exhibited the strongest response, with an IC50 value of 9.6 ± 1.1 nM. CAP further enhanced PPIX-mediated cytotoxicity. Increased ROS generation, enhanced apoptosis, and marked mitochondrial membrane potential disruption were observed particularly in CAP-Light-PPIX-treated cells. Although encapsulation of PPIX within MNCs reduced acute cytotoxicity compared with free PPIX, the nanoplatform retained responsiveness to light and CAP stimulation. These findings demonstrate that CAP potentiates PPIX-mediated photodynamic effects through enhanced oxidative stress and suggest that mesoporous silica-coated magnetic nanoclusters represent a promising platform for controlled photosensitizer delivery in CAP-assisted PDT applications.

Nanosystem-Mediated Phototherapy (PDT/PTT) - Chemodynamic Therapy for Synergistic Antitumor Therapy: Strategies and Advances

This review constructs a refined mechanistic framework to elaborate the complementary mechanisms of PDT and PTT toward CDT in terms of reaction kinetics modulation, endogenous substrate replenishment, and tumor antioxidant defense inhibition, and the key bottlenecks hindering clinical translation.

A Chloroplast-Inspired Theranostic Nanoplatform for Self-Sustaining Oxygen-Elevating Photodynamic Therapy and Glutathione-Triggered Carbon-Centered Radical Synergistic Therapy.

This work reports a novel strategy for developing a theranostic nanoplatform for long-lasting PDT activated by 1530 nm laser irradiation and glutathione (GSH)-triggered carbon-centered radical synergistic therapy that responds specifically to the TME.