Self-Oxygenating Biomimetic Nanoplatform for Synergistic Photodynamic and Photothermal Therapy of Triple-Negative...

Triple-negative breast cancer (TNBC) remains a formidable clinical challenge characterized by its aggressive metastasis and a scarcity of effective treatment strategies. However, photodynamic therapy (PDT) is severely limited by the hypoxic tumor microenvironment, and photothermal therapy (PTT) is restricted by the low photothermal conversion efficiency of the photothermal agents. The photosensitizer IR780 has received widespread attention due to its dual potential in both PDT and PTT, but it suffers from insufficient photostability and is prone to fluorescence quenching. To overcome these challenges, this study constructed a multifunctional self-oxygen-supplying biomimetic nanoparticle platform, named CaO₂@PDA-IR780@CM (CPIC). In this system, calcium peroxide (CaO₂) decomposes in an acidic tumor microenvironment and releases oxygen in situ, effectively alleviating tumor hypoxia and enhancing the PDT efficacy mediated by IR780. Loading IR780 onto polydopamine significantly improved its stability and photothermal performance, achieving a photothermal conversion efficiency of 54.5%, which represents a significant enhancement compared with free IR780. The nanoparticle surface was coated with homologous tumor cell membranes, endowing it with tumor-specific targeting ability. In an orthotopic 4T1 tumor-bearing mouse model, CPIC showed significantly stronger intratumoral fluorescence signals compared with free IR780 and the control nanoparticles without cell membrane coating, thereby confirming its superior tumor targeting efficiency. Furthermore, the combination of PDT/PTT mediated by CPIC significantly suppressed primary tumor growth and effectively inhibited the formation of pulmonary metastatic nodules, highlighting its remarkable translational potential for TNBC treatment.