Self‐Delivery O2‐Ecomonizer to Reverse Antiapoptosis of Hypoxic Tumor for Enhanced Photodynamic Therapy

Abstract Oxygen‐dependent photodynamic therapy (PDT) holds unique advantages on tumor treatment by inducing cell apoptosis, but it is often limited owing to the unfavorable tumor microenvironments. In this study, a self‐delivery O 2 ‐ecomonizer (designated as CeTam) is prepared to relieve hypoxia and reverse antiapoptotic pathway for enhanced photodynamic tumor therapy. Based on Chlorin e6 (Ce6) and Tamoxifen (Tam), CeTam is assembled through intermolecular hydrophobic interaction without any vehicles. Nanosized CeTam has an enhanced stability and improved drug delivery efficiency, which prefers to accumulate at tumor tissue for effective cellular uptake. More importantly, CeTam can effectively inhibit mitochondrial respiration to relieve hypoxia and reduce Bcl‐2 expression to reverse antiapoptotic pathway. As a result, this self‐delivery O 2 ‐ecomonizer successfully regulates the unfavorable tumor microenvironments to enhance the PDT efficacy on tumor elimination. Taken together, this work reports a multifunctional nanoplatform by a simple self‐assembly strategy to remedy the deficiencies of PDT on hypoxic tumor treatment, which can advance the development of individualized biomedicine for precise tumor therapy.