title: Biodegradable polymeric micelle-encapsulated doxorubicin suppresses tumor metastasis by killing circulating tumor cells.
abstract: Circulating tumor cells (CTCs) play a crucial role in tumor metastasis, but it is rare for any chemotherapy regimen to focus on killing CTCs. Herein, we describe doxorubicin (Dox) micelles that showed anti-metastatic activity by killing CTCs. Dox micelles with a small particle size and high encapsulation efficiency were obtained using a pH-induced self-assembly method. Compared with free Dox, Dox micelles exhibited improved cytotoxicity, apoptosis induction, and cellular uptake. In addition, Dox micelles showed a sustained release behavior in vitro, and in a transgenic zebrafish model, Dox micelles exhibited a longer circulation time and lower extravasation from blood vessels into surrounding tissues. Anti-tumor and anti-metastatic activities of Dox micelles were investigated in transgenic zebrafish and mouse models. In transgenic zebrafish, Dox micelles inhibited tumor growth and prolonged the survival of tumor-bearing zebrafish. Furthermore, Dox micelles suppressed tumor metastasis by killing CTCs. In addition, improved anti-tumor and anti-metastatic activities were also confirmed in mouse tumor models, where immunofluorescent staining of tumors indicated that Dox micelles induced more apoptosis and showed fewer proliferation-positive cells. There were decreased side effects in transgenic zebrafish and mice after administration of Dox micelles. In conclusion, Dox micelles showed stronger anti-tumor and anti-metastatic activities and decreased side effects both in vitro and in vivo, which may have potential applications in cancer therapy.
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China. chygong14@163.com.
authors.forename: Senyi
authors.initials: S
authors.lastname: Deng
authors.forename: Qinjie
authors.initials: Q
authors.lastname: Wu
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.forename: Ni
authors.initials: N
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Pang
authors.forename: Xuejing
authors.initials: X
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Bi
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Weijun
authors.initials: W
authors.lastname: Su
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Changyang
authors.initials: C
authors.lastname: Gong
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004343:Drug Implants / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D016896:Treatment Outcome; D015027:Zebrafish
chemical_list: D000903:Antibiotics, Antineoplastic; D004343:Drug Implants; D053769:Nanocapsules; D004317:Doxorubicin