title: Antimetastasis and antitumor efficacy promoted by sequential release of vascular disrupting and chemotherapeutic agents from electrospun fibers.
abstract: The vasculature in tumor microenvironment plays important roles in the tumor growth and metastasis, and the combination of vascular disrupting agents with chemotherapeutic drugs should be effective in inhibiting tumor progression. But the dosing schedules are essential to achieve a balance between vascular collapse and intratumoral uptake of chemotherapeutic agents. In the current study, emulsion and blend electrospinning were used to create compartmental fibers accommodating both combretastatin A-4 (CA4) and hydroxycamptothecin (HCPT). The release durations of CA4 and HCPT were modulated through the structure of fibers for dual drug loadings and the inoculation of 2-hydroxypropyl-β-cyclodextrin in fiber matrices. Under a noncontact cell coculture in Transwell, the sequential release of CA4 and HCPT indicated a sequential killing of endothelial and tumor cells. In an orthotopic breast tumor model, all the CA4/HCPT-loaded fibers showed superior antitumor efficacy and higher survival rate than fibers with loaded individual drug. Compared with fibrous mats with infiltrated free CA4 and fibers with extended release of CA4 for over 30 days, fibers with sustained release of CA4 for 3-7 days from CA4/HCPT-loaded fibers resulted in the most significant antitumor efficacy, tumor vasculature destruction, and the least tumor metastasis to lungs. A judicious selection of CA4 release durations in the combination therapy should be essential to enhance the tumor suppression efficacy and antimetastasis activity.
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, ﻿PR China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Luo
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, ﻿PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, ﻿PR China.
authors.forename: Maohua
authors.initials: M
authors.lastname: Chen
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, ﻿PR China.
authors.forename: Jiaojun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, ﻿PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, ﻿PR China. Electronic address: xhli@swjtu.edu.cn.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D005260:Female; D007773:Lactates / Q000737:chemistry; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000737:chemistry; D013267:Stilbenes / Q000008:administration & dosage* / Q000494:pharmacology; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D007773:Lactates; D013267:Stilbenes; D047392:beta-Cyclodextrins; C527042:hydroxycamptothecinum; C088513:poly(lactic acid-ethylene glycol); D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011092:Polyethylene Glycols; C058728:fosbretabulin; D002166:Camptothecin
keywords: Antitumor efficacy; Electrospun fiber; Release modulation; Tumor metastasis; Vascular disrupting agent