title: Biodegradable polymeric micelles coencapsulating paclitaxel and honokiol: a strategy for breast cancer therapy in vitro and in vivo.
abstract: The combination of chemotherapy drugs attracts more attention in clinical cancer trials. However, the poor water solubility of chemotherapeutic drugs restricts their anticancer application. In order to improve antitumor efficiency and reduce side effects of free drugs, we prepared paclitaxel (PTX) and honokiol (HK) combination methoxy poly(ethylene glycol)-poly(caprolactone) micelles (P-H/M) by solid dispersion method against breast cancer. The particle size of P-H/M was 28.7±2.5 nm, and transmission electron microscope image confirmed that P-H/M were spherical in shape with small particle size. After being encapsulated in micelles, the release of PTX or HK showed a sustained behavior in vitro. In addition, both the cytotoxicity and the cellular uptake of P-H/M were increased in 4T1 cells, and P-H/M induced more apoptosis than PTX-loaded micelles or HK-loaded micelles, as analyzed by flow cytometry assay and Western blot. Furthermore, the antitumor effect of P-H/M was significantly improved compared with PTX-loaded micelles or HK-loaded micelles in vivo. P-H/M were more effective in inhibiting tumor proliferation, inducing tumor apoptosis, and decreasing the density of microvasculature. Moreover, bioimaging analysis showed that drug-loaded polymeric micelles could accumulate more in tumor tissues compared with the free drug. Our results suggested that P-H/M may have potential applications in breast cancer therapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Zhihan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Shihong
authors.initials: S
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Linjiang
authors.initials: L
authors.lastname: Song
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Suleixin
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yi
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Qinjie
authors.initials: Q
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Changyang
authors.initials: C
authors.lastname: Gong
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D008807:Mice, Inbred BALB C; D008823:Micelles; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D001713:Biphenyl Compounds; D004337:Drug Carriers; D017705:Lignans; D008823:Micelles; D017239:Paclitaxel; D011108:Polymers; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: breast cancer; codelivery; honokiol; micelles; paclitaxel