Construction of reduction-responsive photosensitizers based on amphiphilic block copolymers and their application for photodynamic therapy

- Reduction-responsive POEGMA-b-PTPPC6SAM block copolymers were synthesized via RAFT polymerization.
- POEGMA-b-PTPPC6SAM block copolymers could self-assemble into spherical micelles and vesicles.
- POEGMA-b-PTPPC6SAM micelles had a higher photo-toxicity with a lower IC50 (porphyrin concentration below 3 μg/mL).

A novel reduction-responsive porphyrin monomer bearing a disulfide bond (TPPC6SAM) was synthesized, and then it was utilized to construct a series of POEGMA-b-PTPPC6SAM block copolymers via reversible addition-fragmentation transfer (RAFT) polymerization with water-soluble and biocompatible monomer, oligo(ethylene glycol) methyl ether methacrylate (OEGMA). POEGMA-b-PTPPC6SAM block copolymers could self-assemble into spherical micelles and vesicles by varying the mass ratio of hydrophilic block to hydrophobic block. Confocal laser scanning microscopy (CLSM) and flow cytometry showed that POEGMA-b-PTPPC6SAM micelles could effectively accumulate in A549 cells, compared to that of free porphyrin. In addition, minimal dark toxicity and efficacious photo-toxicity in vitro were also evaluated by MTT assay. According to the result of MTT assay, POEGMA-b-PTPPC6SAM block copolymers had a higher photo-toxicity with a lower IC50 (below 3 μg/mL). Thus, reduction-responsive POEGMA-b-PTPPC6SAM block copolymers could well improve the release of porphyrin photosensitizers and enhance the efficiency of PDT.

Schematic illustration for formation of POEGMA-b-PTPPC6SAM aggregates including spherical micelles and vesicles, and their enhanced cellular internalization for PDT.146