Hybrid biointerface engineering nanoplatform for dual-targeted tumor hypoxia relief and enhanced photodynamic therapy

The biointerface engineered PHI@M/L-EApt hybrid nanoplatform is a biomimetic system that combined aptamer-modified liposomes with tumor cell membranes for targeted co-delivery of PFTBA and IR780 to tumor sites. This innovative nanoplatform has been designed to intelligently reverse hypoxic tumor microenvironment and promote the generation of reactive oxygen species, thereby enhancing the effectiveness of PDT and offering great potential for clinical applications. [Display omitted] •Hybrid biointerface engineering platform harnesses tumor-targeting abilities from L-EApt and TMs for specifical delivery.•PHI@M/L-EApt exerts a robust anti-tumor efficacy by reversing hypoxic TME and promoting ROS generation to enhance PDT.•The developed hybrid-membrane biomimetic approach represents an innovative strategy for engineering biointerface.•The newly-designed hybrid nanoplatform demonstrates enormous potential in facilitating the clinical application of PDT. The clinical application of photodynamic therapy (PDT) is limited by the lack of tumor selectivity of photosensitizer (PS) and the hypoxic tumor microenvironment (TME). To address these limitations of PDT, we developed a hybrid engineered biointerface nanoplatform that integrated anti-epidermal growth factor receptor (EGFR)-aptamer (EApt)-modified liposomes with tumor cell membranes (TMs) to create M/L-EApt. M/L-EApt exhibited enhanced stability and significant dual-targeting ability, enabling selectively accumulate in hypoxic tumor regions after systemic infusion. PHI@M/L-EApt, formed by M/L-EApt loaded with an oxygen carrier perfluorotributylamine (PFTBA) and IR780 (a PS), effectively promoted the therapeutic performance of PDT by reversing the hypoxic TME and increasing the accumulation of IR780 at the tumor sites, resulting in a robust anti-tumor efficacy. In vivo results showed that PHI@M/L-EApt treatment effectively suppressed the growth of triple-negative breast tumors in mice. Our findings demonstrated the synergistic effect of oxygen supply and PDT on tumor treatment using PHI@M/L-EApt. This study presented a biomimetic interface engineering strategy and dual-targeted hybrid nanoplatform for relieving hypoxic TME and potentially facilitating the clinical application of PDT.