Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Enhanced antitumor activity of cabazitaxel targeting CD44+ receptor in breast cancer cell line via surface functionalized lipid nanocarriers

Chun-jiang Zhu, Chuan-guo An

Department of Breast and Thyroid Surgery, People's Hospital of Rizhao, Shandong 276825, China;

For correspondence:- Chuan-guo An Email: AnChuanguo1999@gmail.com Tel:+866333365069

Received: 18 January 2016 Accepted: 7 May 2017 Published: 29 June 2017

Citation: Zhu C, An C. Enhanced antitumor activity of cabazitaxel targeting CD44+ receptor in breast cancer cell line via surface functionalized lipid nanocarriers. Trop J Pharm Res 2017; 16(6):1383-1890 doi: 10.4314/tjpr.v16i6.24

© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the properties of surface-functionalized, hyaluronic acid-coated, cabazitaxel-loaded solid lipid nanoparticles (HA-CZ-SLNs) for the treatment of breast cancer.

Methods: HA-CZ-SLNs were prepared by a homogenization method. Nanoparticles were designed for prolonged circulation and slow release of the drug, as well as internalization of the nanocarrier into cancer cells. The nanoparticles were evaluated using dynamic light scattering, in vitro drug release, cell cytotoxicity and uptake studies.

Results: Transmission electron microscopy revealed the resultant particles to be distinct, discrete, spherical cores surrounded by HA shells with a uniform diameter of ~210 nm. In vitro release of CZ followed a biphasic pattern with sustained release throughout the study period, implying efficient delivery for treatment. Increased cytotoxicity was exerted by HA-CZ-SLNs compared with the free drug. More importantly, HA on the surface of nanoparticles interacted with CD44 receptors overexpressed on cancer cells, resulting in increased internalization in MCF-7 cells. Excess free HA competed with this uptake, indicating that nanoparticle uptake was via receptor-mediated endocytosis. This mechanism is expected to result in enhanced therapeutic efficacy for the treatment of breast cancer.

Conclusion: The results indicate prolonged release and enhanced cell penetration, release and cytotoxicity of the drug, thus showing the potential application of the surface-modified nanoparticles for the treatment of breast cancer.

Keywords: Cabazitaxel, Breast cancer, Hyaluronic acid, Nanoparticle, Lipid carrier, Receptor-mediated endocytosis