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

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.

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.

Algae-Integrated Optoelectronic Nanoplatform for Tumor Hypoxia Relief and Enhanced Photodynamic Therapy.

The clinical efficacy of photodynamic therapy (PDT) is fundamentally limited by the scarcity of efficient photosensitizers (PSs) and the oxygen dependence of singlet-oxygen-mediated cytotoxicity. Here we report pentaperylene decaimide selenide (PPD-Se), a nanographene-derived photoelectronic material that functions as a high-performance Type-II photosensitizer. PPD-Se exhibits broadband absorption (300-650 nm), enhanced intersystem crossing enabled by a selenium-induced heavy-atom effect, a small ΔEST (0.50 eV), and a high 1O2 quantum yield (ΦΔ = 0.40). To address hypoxia-limited PDT, PPD-Se nanoparticles were covalently integrated with microalgae to construct an algae@PPD-Se biohybrid, in which PPD-Se is shielded from premature activation yet undergoes glutathione (GSH)-triggered release in the tumor microenvironment. Cleavage of disulfide linkages restores the photosynthetic activity of algae, enabling light-driven O2 production that alleviates local hypoxia and simultaneously boosts PPD-Se-mediated ROS generation. The biohybrid exhibits enhanced intracellular uptake, amplified ROS production, and potent apoptosis induction under white light-emitting diode (LED) irradiation (400-700 nm, 1 mW·cm-2). In vivo, algae@PPD-Se significantly downregulates HIF-1α, restores intra-tumoral oxygenation, and achieves marked tumor growth inhibition without observable systemic toxicity. This study introduces a dual-functional optoelectronic-biological PDT platform that couples a newly designed nanographene photosensitizer with photosynthetic oxygenation, offering a mechanistically driven strategy to overcome the oxygen dependency of PDT.

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

Advances in green-synthesized quantum dot-based nanoplatforms for cancer treatment, photodynamic therapy, photothermal therapy and cancer theranostics

The escalating global cancer burden, particularly in low- and middle-income countries, necessitates safer and more effective therapeutic strategies. The toxicity and environmental issues of traditional heavy-metal-based quantum dots (QDs) have been addressed by green-synthesised QDs, which have become a promising platform for nanomedicine. In photodynamic treatment (PDT), photothermal therapy (PTT), and theranostic applications, the anticancer effectiveness of green-synthesized QDs that are derived from plant extracts, microbes, biomolecules, and biomass waste is critically assessed. Green synthesis techniques, such as hydrothermal and microwave-assisted methods, provide biocompatible QDs with good photostability, tunable optical characteristics, and decreased cytotoxicity. Mechanistically, these QDs generate reactive oxygen species (ROS), induce mitochondrial dysfunction, produce localized hyperthermia upon near-infrared irradiation, and activate apoptotic pathways (such as p53, Bax/Bcl-2, and caspase cascade), leading to selective cancer cell death. Preclinical in vitro and in vivo studies demonstrate potent tumor ablation through passive (EPR effect) and active targeting strategies. Despite these advances, some key setbacks hinder their clinical translation: lack of standardized synthesis protocols, batch-to-batch variability, limited long-term biosafety data, suboptimal targeting efficiency, and regulatory hurdles. Future perspectives include AI-driven optimization, smart theranostic platforms integrating multimodal imaging and therapy, and sustainable circular economy approaches using biowaste. Addressing these challenges through harmonized protocols and rigorous preclinical validation will be essential to realize the full potential of green-synthesized QDs as safe, multifunctional, and effective cancer nanomedicines.

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.