Abstract:
Nowadays, photodynamic therapy(PDT) has become one of the promising and important cancer therapies. 5, 10, 15, 20-Tetraphenyl porphyrin(TPP), a unique and promising photosensitizer which can convert triplet oxygen(
3O
2) into singlet oxygen(
1O
2) after laser illumination, can be used to kill cancer cells. Due to the strong hydrophobicity of porphyrin molecules, porphyrins always need the physical encapsulation by different vehicles. However, the general physical encapsulation not only makes it difficult to quantify the loaded porphyrin content accurately, but also causes aggregation effects after the intracellular release, leading to a compromised PDT effect. Herein, we developed a NIR-triggered pH-responsive amphiphilic block copolymer as to serve as the photosensitizer and drug delivery system(DDS) for the combination of PDT therapy and chemotherapy. The well-defined block copolymer was composed of hydrophilic poly(ethylene glycol)(PEG) block, hydrophobic poly((diisopropylamino)ethyl methacrylate)(PDPA) block and a TPP unit at the junction point between PEG and PDPA. Such a copolymer was synthesized by the combination of RAFT polymerization and click chemistry. The amphiphilic pH-responsive block copolymer(PEG-PDPA-TPP) can self-assemble into spherical micelles in aqueous solution and perform as a perfect drug release platform. It is worthy to notice that the well-designed chemical structure of PEG-PDPA-TPP with TPP at the junction point leads to a relatively regular arrangement of TPP moieties between the hydrophobic and hydrophilic blocks instead of aggregating together, which can reduce the aggregation-induced quenching effect of the photosensitizers, thereby increasing the quantum yield of singlet oxygen. Meanwhile, the Doxorubicin(DOX)-loaded PEG-PDPA-TPP nanoparticles will dissociate under weak acidic conditions and release the drug after entering the cells by endocytosis. Therefore, this pH-responsive TPP-containing block copolymer provides a new strategy for cancer treatment.