title: Losartan loaded liposomes improve the antitumor efficacy of liposomal paclitaxel modified with pH sensitive peptides by inhibition of collagen in breast cancer.
abstract: The dense collagen network in tumors restricts the penetration of drugs into tumors. Free losartan could inhibit collagen, but it would cause hypotension at the dosage of 10 mg/kg/d. In this study, losartan was encapsulated in liposomes (LST-Lip) and the collagen inhibition ability of LST-Lip was investigated. Our results showed the blood pressure was not affected by LST-Lip at the dosage of 2.5 mg/kg every other day. The amount of Evans Blue in tumor in LST-Lip group was 1.98 times of that in control group. Confocal laser scanning microscopy images showed that prior injection of LST-Lip could inhibit collagen and further improve the tumorous accumulation of liposomes modified with TH peptides (AGYLLGHINLHHLAHL(Aib)HHIL-NH2) (TH-Lip) in 4T1 tumors. Compared with control group, the tumor inhibition rate of combined strategy of LST-Lip and paclitaxel loaded TH-Lip (PTX-TH-Lip) was 41.73%, while that of group only treated with PTX-TH-Lip was 14.94%. Masson's trichrome staining confirmed that collagen was inhibited in LST-Lip group. Thus, the administration of LST-Lip in advance could inhibit the collagen in tumors effectively and did not affect the blood pressure, then PTX-TH-Lip injected subsequently could exert enhanced antitumor efficacy. In conclusion, this combined strategy might be promising for breast cancer therapy.
authors.affiliation: a School of Chemical Engineering , Sichuan University , Chengdu , People's Republic of China.
authors.forename: Tai
authors.initials: T
authors.lastname: Xia
authors.affiliation: b Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy , Sichuan University , Chengdu , People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: He
authors.affiliation: b Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy , Sichuan University , Chengdu , People's Republic of China.
authors.forename: Kairong
authors.initials: K
authors.lastname: Shi
authors.affiliation: b Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy , Sichuan University , Chengdu , People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy , Sichuan University , Chengdu , People's Republic of China.
authors.forename: Qianwen
authors.initials: Q
authors.lastname: Yu
authors.affiliation: b Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy , Sichuan University , Chengdu , People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: b Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy , Sichuan University , Chengdu , People's Republic of China.
authors.forename: Qianyu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: b Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy , Sichuan University , Chengdu , People's Republic of China.
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.affiliation: a School of Chemical Engineering , Sichuan University , Chengdu , People's Republic of China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Ma
authors.affiliation: c West China School of Preclinical and Forensic Medicine , Sichuan University , Chengdu , People's Republic of China.
authors.forename: Ji
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D003094:Collagen / Q000037:antagonists & inhibitors*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D019808:Losartan / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D010455:Peptides; D003094:Collagen; D019808:Losartan; D017239:Paclitaxel
keywords: Losartan loaded liposomes; breast cancer; collagen inhibition; combined strategy; enhanced antitumor efficacy