A novel micelle based on heparosan and deoxycholic acid (DOCA) conjugate (HD) as drug carrier was reported here. As the surface was negatively charged, this micelle could resist serum adsorption, showing favorable stability. Moreover, fluorescence observation confirmed that it was able to deliver model hydrophobic drug doxorubicin (DOX) into HeLa cells efficiently. The DOX-loaded micelles showed sustained release behavior at pH 7.4, and accelerated release behavior at pH 5.0 or in the presence of β-glucuronidase, which over-expressed in tumor cells. In vitro cytotoxicity assay demonstrated that the half-maximal inhibitory concentration (IC50) of DOX-loaded micelles against HeLa cells was much lower than that of COS7 cells, showing significant therapeutic distinction between tumor cells and normal cells. Combining with the good biocompatibility and biodegradability of heparosan, this micelle may be promising in clinical application for targeted drug delivery.
Zhengqi Zha,Yinghua Miao,Huiling Tang,Daniela D. Herrera-Balandrano,Hongping Yin,Su-Yan Wang
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.
In this study, we reported a redox-responsive drug delivery system (DDS) based on heparosan and deoxycholic acid conjugates (HSDs) for effective treatment of laryngopharyngeal carcinoma. The amphiphilic HSDs can self-assemble into stable nanoscale micelles in aqueous medium with favorable drug loading capacity for doxorubicin (DOX). The HSD micelles can exhibit glutathione (GSH)-triggered drug release behavior and reach a nearly 100% release rate in a high GSH level (10 mM) environment. Moreover, FaDu cancer cells can internalize HSD micelles by clathrin-mediated endocytosis, which is energy dependent, fast, and effective. The DOX@HSD induced inhibition of FaDu cancer cells can achieve a minimum of 10-fold selectivity relative to that of COS-7 normal cells. Overall, the redox-responsive DDSs show good biocompatibility and are promising in the clinical treatment of laryngopharyngeal carcinoma.
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