l-Peptide functionalized dual-responsive nanoparticles for controlled paclitaxel release and enhanced apoptosis in breast cancer cells

Drug Delivery

Jianrong Wu¹  Heyu Li¹  Haijun Wang¹  Shiwei Niu¹  Junzi Wu¹  Qianqian Qian¹  Limin Zhu¹  Hong Zheng²  David H. Bremner³ 

[1] College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, PR China;Department of Experimental Animal Science, Kunming Medical University, Kunming, PR Chin;School of Science, Engineering and Technology, Abertay University, Dundee, Scotland, UK;

关键词: -Peptide;    dual-responsive;    apoptosis;    nanoparticles;    anticancer efficacy;   

DOI  :  10.1080/10717544.2018.1477863

来源: publisher

【 摘 要 】

Nanoparticles and macromolecular carriers have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by their enhanced permeability and retention effect. However, the therapeutic efficacy of nanoscale anticancer drug delivery systems is severely truncated by their low tumor-targetability and inefficient drug release at the target site. Here, the design and development of novel l-peptide functionalized dual-responsive nanoparticles (l-CS-g-PNIPAM-PTX) for active targeting and effective treatment of GRP78-overexpressing human breast cancer in vitro and in vivo are reported. l-CS-g-PNIPAM-PTX NPs have a relative high drug loading (13.5%) and excellent encapsulation efficiency (74.3%) and an average diameter of 275 nm. The release of PTX is slow at pH 7.4 and 25 °C but greatly accelerated at pH 5.0 and 37 °C. MTT assays and confocal experiments showed that the l-CS-g-PNIPAM-PTX NPs possessed high targetability and antitumor activity toward GRP78 overexpressing MDA-MB-231 human breast cancer cells. As expected, l-CS-g-PNIPAM-PTX NPs could effectively treat mice bearing MDA-MB-231 human breast tumor xenografts with little side effects, resulting in complete inhibition of tumor growth and a high survival rate over an experimental period of 60 days. These results indicate that l-peptide-functionalized acid – and thermally activated – PTX prodrug NPs have a great potential for targeted chemotherapy in breast cancer.

【 授权许可】

CC BY