Hyaluronic Acid Capped, Irinotecan and Gene Co-Loaded Lipid-Polymer Hybrid Nanocarrier-Based Combination Therapy Platform for Colorectal Cancer

• Main Authors: Wang Z, Zang A, Wei Y, An L, Hong D, Shi Y, Zhang J, Su S, Fang G
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-03-01
• Series: Drug Design, Development and Therapy
• Subjects: colorectal cancer; combination therapy; lipid-polymer hybrid nanoparticles; hyaluronic acid; irinotecan
• Online Access: https://www.dovepress.com/hyaluronic-acid-capped-irinotecan-and-gene-co-loaded-lipid-polymer-hyb-peer-reviewed-article-DDDT
• ISSN: 1177-8881

Zhiyu Wang, Aimin Zang, Yaning Wei, Lin An, Dan Hong, Yan Shi, Jingnan Zhang, Shenyong Su, Guotao Fang Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding 071000, People’s Republic of ChinaCorrespondence: Guotao FangDepartment of Medical Oncology, Affiliated Hospital of Hebei University, No. 648 Dongfeng East Road, Lianchi District, Baoding 071000, Hebei Province, People’s Republic of ChinaTel [phone]Email [e-mail]: The current approach for treating colorectal cancer favors the use of drug and gene combination therapy, and targeted nano-systems are gaining considerable attention for minimizing toxicity and improving the efficacy of anticancer treatment. The aim of this study was to develop ligand-modified, irinotecan and gene co-loaded lipid-polymer hybrid nanocarriers for targeted colorectal cancer combination therapy.Methods: Hyaluronic acid modified, irinotecan and gene co-loaded LPNs (HA-I/D-LPNs) were prepared using a solvent-evaporation method. Their average size, zeta potential, drug and gene loading capacity were characterized. The in vitro and in vivo gene transfection and anti-tumor ability of this nano-system were evaluated on colorectal cancer cells and mice bearing colorectal cancer model.Results: HA-I/D-LPNs had a size of 182.3 ± 5.1, over 80% drug encapsulation efficiency and over 90% of gene loading capacity. The peak plasma concentration (Cmax) and half-life (T1/2) achieved from HA-I/D-LPNs were 41.31 ± 1.58 μg/mL and 12.56 ± 0.67 h. HA-I/D-LPNs achieved the highest tumor growth inhibition efficacy and the most prominent transfection efficiency in vivo.Conclusion: HA-I/D-LPNs exhibited the most remarkable tumor inhibition efficacy and best gene transfection efficiency in the tumor, which could prove the effects of the drug and gene combination therapy.Keywords: colorectal cancer, combination therapy, lipid-polymer hybrid nanoparticles, hyaluronic acid, irinotecan