Folate-targeted nanostructured chitosan/chondroitin sulfate complex carriers for enhanced delivery of bortezomib to colorectal cancer cells

作者：Zar Chi Soe, Bijay Kumar Poudel, Hanh Thuy Nguyen, Raj Kumar Thapa, Wenquan Ou, Milan Gautam, Kishwor Poudel, Sung Giu Jin, Jee‐Heon Jeong, Sae‐Kwang Ku, Han‐Gon Choi, Chul Soon Yong, Jong Oh Kim · 发表于：Asian Journal of Pharmaceutical Sciences · 年份：2018 · DOI：10.1016/j.ajps.2018.09.004 · 被引用次数：126 · 研究领域：Nanoparticle-Based Drug Delivery、Dendrimers and Hyperbranched Polymers、RNA Interference and Gene Delivery

Folate-targeting self-assembled nanoparticles (NPs) using biocompatible and biodegradable natural polymers chitosan (Cs) and chondroitin sulfate (Chs) were developed to address the major challenge in cancer treatment, the selective delivery of nanoparticles to the target site. In this study, we successfully incorporated a hydrophobic drug, bortezomib (Bor), into folic acid (FA)-conjugated Cs/Chs self-assembled NPs (Bor/Cs/Chs-FA) for colorectal cancer therapy. The particle size and polydispersity index of Bor/Cs/Chs-FA were ∼196.5 ± 1.2 nm and ∼0.21 ± 0.5, respectively. A pH-dependent release profile was observed, facilitating cancer cell-targeted drug release under an acidic tumor microenvironment. Moreover, in vitro data revealed enhanced cellular uptake and apoptosis in folate receptor-expressing colorectal cancer cells (HCT-116 and HT-29) as compared to that in lung cancer cells (A549), which do not express folate receptors. Furthermore, intravenous administration of Bor/Cs/Chs-FA in a HCT-116 bearing xenograft mouse model showed that the NPs were a safe and effective drug delivery system. The results suggest that folate-targeted nanoparticle can be effectively applied for efficient chemotherapy of colorectal cancer.