title: Functional-segregated coumarin-containing telodendrimer nanocarriers for efficient delivery of SN-38 for colon cancer treatment.
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.
authors.affiliation: Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States; Department of Applied Chemistry, Science College, China Agricultural University, Beijing 100193, China.
authors.forename: Gaofei
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
authors.forename: Changying
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
authors.forename: Dandan
authors.initials: D
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Applied Chemistry, Science College, China Agricultural University, Beijing 100193, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States. Electronic address: luoj@upstate.edu.
authors.forename: Juntao
authors.initials: J
authors.lastname: Luo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003374:Coumarins / Q000032:analysis*; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers; D006801:Humans; D000077146:Irinotecan; D056004:Molecular Dynamics Simulation; D049329:Nanostructures
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D050091:Dendrimers; D004337:Drug Carriers; D000077146:Irinotecan; C030123:coumarin; D002166:Camptothecin
keywords: Drug delivery; Irinotecan; Micelles; Nanomedicine; SN-38