A supramolecular nanoparticle system based on beta-cyclodextrin-conjugated poly-L-lysine and hyaluronic acid for co-delivery of gene and chemotherapy agent targeting hepatocellular carcinoma

作者：Xiong, Qingqing^*; Cui, Mangmang; Bai, Yang; Liu, Yuanyuan; Liu, Di; Song, Tianqiang^*

来源：Colloids and Surfaces B: Biointerfaces , 2017, 155: 93-103.

DOI：10.1016/j.colsurfb.2017.04.008

• Co-delivery
• Supramolecular nanoparticles
• Hyaluronic acid
• Cyclodextrin
• Hepatocellular carcinoma

A novel supramolecular nanoparticle system with core-shell structure was designed based on beta-cyclodextrin-conjugated poly-L-lysine (PLCD) and hyaluronic acid for co-delivery of gene and chemotherapy agent targeting hepatocellular carcinoma (HCC). PLCD was synthesized by the conjugation of monoaldehyde activated beta-cyclodextrin with poly-L-lysine via Shift's base reaction. Doxorubicin, as a model therapeutic drug, was included into the hydrophobic cavity of beta-cyclodextrin in PLCD through host-guest interaction. OligoRNA, as a model gene, was further condensed into the inclusion complexes by electrostatic interaction to form oligoRNA and doxorubicin co-loaded supramolecular nanoparticle system. Hyaluronic acid, which is often over-expressed by HCC cells, was coated on the surface of the above nanoparticles to construct HCC-targeted nanoparticle system. These nanoparticles had regular spherical shape with classic "core-shell" structure, and their size and zeta potential were 195.8 nm and 22.7 mV, respectively. The nanoparticles could effectively deliver doxorubicin and oligoRNA into HCC cells via CD44 receptor-mediated endocytosis and significantly inhibit the cell proliferation. In the nude mice bearing MHCC-97H tumor, the nanoparticles could be efficiently accumulated in the tumor, suggesting their strong hepatoma-targeting capability. These findings demonstrated that this novel supramolecular nanoparticle system had a promising potential for combining gene therapy and chemotherapy to treat HCC.

• 出版日期2017-7-1
• 单位天津医科大学