期刊
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
卷 23, 期 1, 页码 13-21出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10837450.2016.1265553
关键词
Losartan loaded liposomes; collagen inhibition; enhanced antitumor efficacy; combined strategy; breast cancer
资金
- National Natural Science Foundation of China [81373337]
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 10mg/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 2.5mg/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.
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