anti-tumor effect via passive anti-angiogenesis of pegylated liposomes encapsulating doxorubicin in drug resistant tumor.聚乙二醇脂质体的抗肿瘤效应通过被动抗血管生成封装阿霉素耐药t.pdf

International Journal of Pharmaceutics 509 (2016) 178–187 Contents lists available at ScienceDirect International Journal of Pharmaceutics journa l home page : www.e /locate/ijpharm Anti-tumor effect via passive anti-angiogenesis of PEGylated liposomes encapsulating doxorubicin in drug resistant tumors Golam Kibria, Hiroto Hatakeyama, Yusuke Sato, Hideyoshi Harashima* Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo 060-0812, Japan A R T I C L E I N F O A B S T R A C T Article history: Received 26 February 2016 The PEGylated liposomal (PEG-LP) Doxorubicin, PEG-LP (DOX), with a diameter of around 100 nm, Received in revised form 24 April 2016 accumulates in tumors via the enhanced permeability and retention (EPR) effect, and is used clinically for Accepted 24 May 2016 the treatment of several types of cancer. However, there are a number of tumor types that are resistant to Available online 24 May 2016 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 Keywords: cancer, H69AR; renal cell carcinoma, OSRC-2) as observed in the xenograft model. Unexpectedly, tumor PEGylated liposome growth was suppressed in a DOX-resistant breast cancer (MDA-MB-231) xenograft model. We Doxil