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590. Anti-EGFR Aptamer-Conjugated Lipoplexses, a Novel Gene Delivery Strategy for Triple Negative Breast Cancer Therapy

Min Woo Kim, H. Jeong, Seong Jae Kang, I. Jeong, Moon-Jung Choi, Young Myoung You, Chan-Su Im, Y. Park

2016

Abstract

Basal-like breast cancer, one of the subtypes of breast cancer, have been focused because of their pathologic features like absence of three common markers such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu). The basal subtype is also called triple negative breast cancer (TNBC) and has shown a higher rate of metastasis, poor prognosis, unresponsive to therapy. Especially, their lack of HER2 expression and aggressive progression make it difficult to utilize HER2-targeted therapeutics and diagnostics to the metastatic TNBC. In this study, theranostic cationic liposomes consisting of quantum dots (QDs) and O,O’-dimyristyl-N-lysyl glutamate (DMKE) were prepared. The quantum dot-incorporating cationic liposomes (QCLs) were then complexed with Bcl-2 and PKC- λ/ι small interfering RNA (siRNA) for silencing of genes inhibiting apoptosis, and promoting cell proliferation, and cell migrations. The cationic characteristics of the QCLs provided an effective siRNA transfection in vitro, but it had limitations in in vivo applications. To enhance cancer-directed delivery, epidermal growth factor receptor (EGFR) aptamer-polyethylene glycol conjugates were inserted into the prepared QCLs. The advantages of the two-step strategy of QCL preparation include effective QD formulation, in vivo long circulation, and TNBC specific gene silencing. This study suggests that EGFR aptamer-conjugated QCL can be utilized as a useful theranostic…

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