Herceptin-conjugated temperature-sensitive immunoliposomes encapsulating gemcitabine for breast cancer.

Dae Hwan Shin, Min-Ji Koo, Jung Seok Kim, Jin-Seok Kim

Index: Arch. Pharm. Res. 39 , 350-8, (2016)

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Abstract

Gemcitabine (2',2'-difluorodeoxycytidine, GCT) is an analog of deoxycytidine with cytotoxicity for breast cancer cells. However, because of its hepatotoxicity and other side effects, an efficient drug delivery system is needed for better therapeutic outcomes. A temperature-sensitive PEGylated immunoliposome (TSL) with trastuzumab (or Herceptin) attached encapsulating GCT (Her-PEG-TSL-GCT) was prepared. The mean diameter of the liposome was about 200 nm and the prepared immunoliposome showed the capacity to deliver the payload to the hyperthermic environment. The actual number of antibody molecules attached to one single liposome is about 19, with the GCT encapsulation efficiency of 54.6 ± 3.50 %. This immunoliposome shows a temperature-dependent drug release at around 41-43 °C. Anticancer activity of Her-PEG-TSL-GCT was determined using HER-2 expressing breast cancer cells, SK-BR-3, in vitro and resulted in increased cytotoxicity compared to free GCT (IC20 11.7 nM) or conventional liposome lacking the targeting antibody. In conclusion, these data show that improved delivery of GCT to breast cancer cells can be achieved by Her-PEG-TSL-GCT in vitro, and this strategy could be used for breast cancer therapy with further studies.