Enhancing Photochemical Internalization of DOX through a Porphyrin-based Amphiphilic Block Copolymer

Drug resistance is a primary obstacle that seriously reduces the therapy efficiency of most chemotherapeutic agents. To address this issue, the photochemical internalization (PCI) was employed to help the anticancer drug escape from lysosome and improve their translocation to the nucleus. A pH-sensitive porphyrin-based amphiphilic block copolymer (PEG₁₁₃-b-PCL₅₄-a-porphyrin) was synthesized, which was acted not only as a carrier for the delivery of DOX but also as a photosensitizer for PCI. PEG₁₁₃-b-PCL₅₄-a-porphyrin as a drug carrier exhibited a higher drug loading capacity, entrapment efficiency, and DOX release content. The PCI effect of PEG₁₁₃-b-PCL₅₄-a-porphyrin was studied by confocal laser scanning microscopy, and the results showed that most of DOX could be translocated into the nucleus for DOX-loaded PEG₁₁₃-b-PCL₅₄-a-porphyrin micelles. Moreover, the IC₅₀ of pH-sensitive DOX-loaded PEG₁₁₃-b-PCL₅₄-a-porphyrin micelles was much lower than that of its counterpart without pH-responsiveness, DOX-loaded PEG₁₁₃-b-PCL₅₄-porphyrin micelles. Therefore, this drug delivery system based on pH-sensitive porphyrin-containing block copolymer would act as a potential vehicle for overcoming drug resistance in chemotherapy.