A tenascin C targeted nanoliposome with navitoclax for specifically eradicating of cancer-associated fibroblasts

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• 作者：Binlong Chen ; MSc^a ; ^b ; Zhaoyang Wang ; MPharm^a ; ^b ; Jing Sun ; MPharm^a ; ^b ; Qin Song ; MSc^a ; ^b ; Bing He ; PhD^a ; ^b ; Hua Zhang ; PhD^a ; Xueqing Wang ; PhD^a ; Wenbing Dai ; PhD^a ; ^{pawpaw009@126.com" class="auth_mail" title="E-mail the corresponding author} ; Qiang Zhang ; PhD^a ; ^b ; ^{zqdodo@bjmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cancer-associated fibroblasts ; Tenascin C ; Navitoclax ; Tumor microenvironment ; Nanoliposome ; Target delivery
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：12
• 期：1
• 页码：131-141
• 全文大小：2273 K

文摘

Cancer-associated fibroblasts (CAFs) play a vitally important role during tumor progression. Navitoclax (Nav) can specifically induce apoptosis in CAFs. The present study aims to develop a novel CAF-targeted nanoliposome for cancer therapy. Nav-loaded nanoliposomes modified with peptide FH (FH-SSL-Nav), which specifically binds to tenascin C, a protein mainly expressed by CAFs, were formulated and characterized. Several experiments were performed to evaluate CAFs selective apoptosis, targeting and eradicating. Compared with SSL-Nav, FH-SSL-Nav achieved higher cellular uptake, and exhibited stronger cytotoxicity in vitro. The in vivo tumor stroma targeting effect was further confirmed by near infrared imaging. Accordingly, FH-SSL-Nav displayed improved tumor growth inhibition by eradicating CAFs in Hep G2 tumor-bearing nude mice model. In conclusion, FH-SSL-Nav could achieve targeting delivery of Nav to CAFs in vitro and in vivo, and may offer a potential strategy for cancer therapy based on tumor stroma.

From the Clinical Editor

The progression of cancer cells often depends on the underlying tumor microenvironment, in which cancer-associated fibroblasts play an important role. In this article, the authors developed targeted therapy against CAFs using liposomes as carriers. This new modality was shown to be more effective in tumor killing both in vitro and in vivo. The finding may open a new era in cancer therapy.