title: Epirubicin loaded with propylene glycol liposomes significantly overcomes multidrug resistance in breast cancer.
abstract: Multidrug resistance (MDR) is one of the major reasons for the failure of cancer chemotherapy. A newly reported liposome carrier, propylene glycol liposomes (EPI-PG-liposomes) were made to load epirubicin (EPI) which enhanced EPI absorption in MDR tumor cells to overcome the drug resistance. MDA-MB 435 and their mutant resistant (MDA-MB 435/ADR) cells were used to examine the cellular uptake and P-gp function in vitro for EPI-PG-liposomes by fluorescence microscopy and FCM, respectively. Mammary tumor model was also established to investigate the tumor growth inhibition and pharmacodynamics of EPI-PG-liposomes in vivo. Morphology evaluation showed that EPI-PG-liposomes had a homogeneous spherical shape with an average diameter of 182 nm. Based on cell viability assay, fluorescent microscopy examination, and EPI uptake assay, EPI-PG-liposomes exhibited an effective growth inhibition not only in MDA-MB-435 cells, but also in MDA-MB 435/ADR cells. EPI-PG-liposomes have high permeability not only on tumor cell membrane, but also on cell nucleus membrane. P-gp function assay showed that the anticancer action of EPI-PG-liposomes was not related to P-gp efflux pump, suggesting that PG-liposomes would not affect the normal physiological functions of membrane proteins. EPI-PG-liposomes also showed a better antitumor efficacy compared to EPI solution alone. With high entrapment efficiency, spherical morphology and effective inhibition on MDR cancer cells, EPI-PG-liposomes may represent a better chemotherapeutic vectors for cancer targeted therapy.
authors.affiliation: Wenzhou Medical College, Wenzhou City, Zhejiang Province 325035, China. zhaoyz@mzmc.edu.cn
authors.forename: Ying-Zheng
authors.initials: YZ
authors.lastname: Zhao
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Dai
authors.forename: Cui-Tao
authors.initials: CT
authors.lastname: Lu
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Shen
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Jin
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Lv
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.forename: Pin-Tong
authors.initials: PT
authors.lastname: Huang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019946:Propylene Glycol / Q000008:administration & dosage / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D015251:Epirubicin; D019946:Propylene Glycol