RRC ID 62744
著者 Kibria G, Hatakeyama H, Sato Y, Harashima H.
タイトル Anti-tumor effect via passive anti-angiogenesis of PEGylated liposomes encapsulating doxorubicin in drug resistant tumors.
ジャーナル Int J Pharm
Abstract The PEGylated liposomal (PEG-LP) Doxorubicin, PEG-LP (DOX), with a diameter of around 100nm, accumulates in tumors via the enhanced permeability and retention (EPR) effect, and is used clinically for the treatment of several types of cancer. However, there are a number of tumor types that are resistant to DOX. We report herein on a unique anti-tumor effect of PEG-LP (DOX) in a DOX-resistant tumor xenograft model. PEG-LP (DOX) failed to suppress the growth of the DOX-resistant tumors (ex. non-small cell lung cancer, H69AR; renal cell carcinoma, OSRC-2) as observed in the xenograft model. Unexpectedly, tumor growth was suppressed in a DOX-resistant breast cancer (MDA-MB-231) xenograft model. We investigated the mechanism by which PEG-LP (DOX) responses differ in different drug resistant tumors. In hyperpermeable OSRC-2 tumors, PEG-LP was distributed to deep tumor tissues, where it delivers DOX to drug-resistant tumor cells. In contrast, extracellular matrix (ECM) molecules such as collagen, pericytes, cancer-associated fibroblasts render MDA-MB-231 tumors hypopermeable, which limits the extent of the penetration and distribution of PEG-LP, thereby enhancing the delivery of DOX to the vicinity of the tumor vasculature. Therefore, a remarkable anti-angiogenic effect with a preferential suppression in tumor growth is achieved. Based on the above findings, it appears that the response of PEG-LP (DOX) to drug-resistant tumors results from differences in the tumor microenvironment.
巻・号 509(1-2)
ページ 178-187
公開日 2016-7-25
DOI 10.1016/j.ijpharm.2016.05.047
PII S0378-5173(16)30436-7
PMID 27234700
MeSH Angiogenesis Inhibitors / chemistry* Angiogenesis Inhibitors / pharmacology Animals Antibiotics, Antineoplastic / chemistry Antibiotics, Antineoplastic / pharmacology* Cell Line, Tumor Doxorubicin / analogs & derivatives* Doxorubicin / chemistry Doxorubicin / pharmacology Drug Carriers / chemistry Drug Resistance, Neoplasm / drug effects* Female Humans Liposomes / chemistry* Male Mice Mice, Inbred BALB C Mice, Nude Polyethylene Glycols / chemistry* Polyethylene Glycols / pharmacology Tumor Microenvironment / drug effects
IF 4.845
リソース情報
ヒト・動物細胞 HeLa OS-RC-2(RCB0735)