Preparation of zinc phthalocyanine-loaded amphiphilic phosphonium chitosan nanomicelles for enhancement of photodynamic therapy efficacy.

To increase the solubility and the encapsulation of zinc phthalocyanine (ZnPc) photosensitizer for photodynamic therapy (PDT), a positively charged amphiphilic phosphonium chitosan nanomicelle with multi-benzene structure was developed, and its application to PDT was explored. N-acetyl-l-phenylalanine-(4-carboxybutyl) triphenylphosphonium bromide chitosan (CTPB-CS-NAP), a chitosan derivative with tunable amphiphilicity, was synthesized first. ZnPc was encapsulated in CTPB-CS-NAP at the critical micelle concentration (CMC) of 4.898 mg/L by a hydrophobic self-assembly method to form ZnPc-loaded nanomicelles (ZnPc@CTPB-CS-NAP). The method gives the highest encapsulation efficiency and drug loading of 89.4 % and 22.3 %, respectively. ZnPc@CTPB-CS-NAP is stably dispersed in aqueous solution and shows the average particle size of 103±5 nm. PDT experiments suggest the phototoxicity of ZnPc@CTPB-CS-NAP is much higher than that of ZnPc, but no obvious dark cytotoxicity is observed. Our study has provided a new strategy for improving the photodynamic therapy efficacy of hydrophobic photosensitizer by the encapsulation with chitosan derivative carriers.