Gemcitabine–camptothecin conjugates: a hybrid prodrug for controlled drug release and synergistic therapeutics. (6th July 2017)

• Record Type: Journal Article
• Authors: Hou, Meili; Xue, Peng; Gao, Yong-E.; Ma, Xiaoqian; Bai, Shuang; Kang, Yuejun; Xu, Zhigang
• Is Part Of: Biomaterials science. Volume 5:Number 9(2017:Sep.)
• Page Start: 1889
• Page End: 1897
• Publication Date: 2017-07-06
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/c7bm00382j
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : Self-assembled small molecule prodrug loaded with gemcitabine and camptothecin and responsive to reductive tumour microenvironment for combination cancer chemotherapy. Abstract : Drug self-delivery systems represent an important approach to enhance the therapeutic efficacy for cancer therapy. We report the design, synthesis and characterization of a new amphiphilic small molecule prodrug based on two types of anticancer drugs, the hydrophilic gemcitabine and hydrophobic camptothecin, linked by a disulfide bond and abbreviated as GT–CPT. The obtained amphiphilic prodrug conjugates self-assembled into nanoparticles in water and showed strong micellar stability and excellent blood compatibility in vivo . The GT–CPT prodrug conjugates could realize precise drug loading as high as ∼75 wt% demonstrating a carrier-free model for efficient drug delivery. Furthermore, the reduction-responsive disulfide bond enabled controlled drug release in the presence of tumour-specific microenvironment. It was found that each of these hybrid drug components (CPT and GT) not only showed enhanced cytotoxicity individually but also exhibited a prominent synergistic effect on HeLa and MCF-7 cancer cells. This study demonstrated the promising potential of this stimuli-responsive hybrid prodrug conjugate for highly efficient co-delivery of multiple anticancer chemotherapeutics, which could inspire further applications using such hybrid prodrug conjugates for combination cancer chemotherapy.