Preparation of Porphyrin-Based Unimolecular Micelles for Synergistic Photodynamic Therapy and Radiotherapy

Polymeric carriers have been widely used in biomedical fields because of their strong structural tunability and biocompatibility, which often proximately determine the in vivo behavior of the drug and are crucial in practical application. In this work, porphyrin-based unimolecular micelles with an average diameter less than 20 nm are developed by light-mediated bromine–iodine transformation reversible-deactivation radical polymerization (BIT-RDRP) for synergistic photodynamic therapy (PDT) and radiotherapy (RT). Tetraphenylporphyrin is designed as a four-arm initiator to afford the PDT function, which is employed to regulate the sequential polymerization of hydrophobic and hydrophilic monomers to produce star-shaped amphiphilic copolymers, followed by self-assembly in water to form unimolecular micelles. A functional monomer containing triplet pyridine ligand is prepared and introduced during the polymerization, which is to combine the radionuclide ¹⁷⁷Lu to provide the RT function. The as-prepared unimolecular micelles exhibit high-temperature and pH stability, as expected. Satisfactory accumulation and retention efficiency in tumors and fast metabolism in organs are achieved, and PDT and RT can be conducted simultaneously to enhance the therapeutic effect toward tumors. This work provides a polymeric drug with bimodal therapy, including radiotherapy, which is expected to be competitive in the field of tumor treatment.