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

Abstract

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.