Functional-segregated coumarin-containing telodendrimer nanocarriers for efficient delivery of SN-38 for colon cancer treatment. (15th July 2015)

• Record Type: Journal Article
• Authors: Xu, Gaofei; Shi, Changying; Guo, Dandan; Wang, Lili; Ling, Yun; Han, Xiaobing; Luo, Juntao
• Is Part Of: Acta biomaterialia. Volume 21(2015)
• Page Start: 85
• Page End: 98
• Publication Date: 2015-07-15
• Subjects: Micelles -- Irinotecan -- SN-38 -- Drug delivery -- Nanomedicine; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2015.04.021
• Languages: English
• ISSNs: 1742-7061

Abstract

Graphical abstract: Abstract: Four coumarin-containing telodendrimers (denoted as P-I, P-II, P-III and P-IV) were designed and synthesized to self-assemble into the corresponding nanoparticles. Of those, two nanoparticles (P-II and P-IV micelles) were screened and selected for targeted drug delivery of 7-ethyl-10-hydroxy camptothecin (SN-38), a prominent and efficacious anticancer agent, for the treatment of colon cancers. The nanoparticle encapsulation significantly increased the solubility of SN-38 in aqueous solution. Dynamic light scattering (DLS) showed the size of these SN-38 nanoparticles to be around 50 nm, and rod-shaped micelles were observed using transmission electron microscopy (TEM). These two novel nanoformulations of SN-38/P-II and SN-38/P-IV were found to exhibit similar in vitro cytotoxic activity against colon cancer cells as the free drug (SN-38 in DMSO) and were 500-fold more potent than irinotecan (a prodrug of SN-38). In addition, near infrared fluorescent (NIRF) optical imaging was utilized to monitor the tumor targeted delivery of SN-38/NPs via co-loading a NIRF dye. It was demonstrated that these NPs preferentially accumulated in tumors when compared to healthy tissue. A pharmacokinetics study showed that SN-38 micelle formulations had a longer circulating time in blood than irinotecan. Furthermore, SN-38 loaded nanoformulations exhibit superior anti-tumor efficacy when compared with irinotecan at equivalent SN-38 dose in HT-29 human colon cancer xenograft models.