Uptake and light-induced cytotoxicity of hyaluronic acid-grafted liposomes containing porphyrin in tumor cells

Abstract

Porphyrins are used in clinic as the photosensitizers for cancer treatment. However, most porphyrins tend to form aggregates in aqueous solution due to their hydrophobicity, which results in significantly reduced photocytotoxicities. Therefore, their applications in clinic are limited. To overcome these disadvantages, drug-carriers are designed for the delivery of porphyrins. In this study, we designed the surface modified liposomes for porphyrin delivery. Four types of porphyrins were loaded in liposome separately. We systemically investigated the porphyrin-containing liposomes in terms of their physicochemical properties as well as light-responsive properties. The hyaluronic acid derivative with aldehyde group was used to modify the liposome-porphyrin via the “click” reaction in order to enhance the uptake in CD44 overexpressed cancer cells. The results showed that 10,15,20-tetrakis(4-hydroxyphenyl) porphyrin (p-OH) had highest loading efficiency. The liposomes with p-OH showed highest toxicity to the cells with or without light exposure. The uptake of hyaluronic acid (HA) coated Lip-p-OH was proved to be specific to MDA-MB-231 cells by pretreating the cells with natural HA polymer as the block agent. This study provided an efficient strategy to enhance the cytotoxicity of porphyrin in aqueous solution, and to increase the affinity of porphyrin to the cancer cells.