Heparosan-based self-assembled nanocarrier for zinc(II) phthalocyanine for use in photodynamic cancer therapy.

Zinc(II) phthalocyanine (ZnPc) is a promising photosensitizer in photodynamic therapy (PDT) for melanoma treatment. However, the poor solubility of ZnPc limits its application. To overcome this limitation, heparosan (HP)-based nanoparticles were prepared by anchoring the l-lysine-linked α-linolenic acid branch to the carboxylic acid group to produce amphiphilic conjugates named heparosan with an l-lysine-linked α-linolenic acid branch (HLA). HLA conjugates could self-assemble into spherical nanoparticles in aqueous media and encapsulate ZnPc to form HLA-ZnPc nanoparticles. The cellular uptake of ZnPc could be improved by HLA carriers. These nanoparticles presented excellent photodynamic-mediated toxicity against mouse melanoma cells (B16) by markedly upregulating the intracellular reactive oxygen species (ROS) levels while showing no cytotoxicity to either B16 or normal cells (L02 and HK-2 cells) in the dark. Furthermore, HLA-ZnPc displayed excellent stability in both powder and Roswell Park Memorial Institute (RPMI) 1640 medium, indicating its promise for application in drug delivery and PDT. These results revealed a strategy for HP-based enhancement of ZnPc in PDT efficacy.