Synergistic active targeting of dually integrin α_vβ₃/CD44-targeted nanoparticles to B16F10 tumors located at different sites of mouse bodies

详细信息    查看全文

• 作者：Sanjun Shi ; ^{shisanjuns@163.com" class="auth_mail" title="E-mail the corresponding author} ; Min Zhou ; Xin Li ; Min Hu ; Chenwen Li ; Min Li ; Fangfang Sheng ; Zhuoheng Li ; Guolin Wu ; Minghe Luo ; Huanhuan Cui ; Ziwei Li ; Ruoqiu Fu ; Mingfeng Xiang ; Jing Xu ; Qian Zhang ; Laichun Lu ; ^{lulab2014@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hyaluronan ; Tetraiodothyroacetic acid ; Docetaxel ; Dual-targeting delivery system ; Synergistic active targeting
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 August 2016
• 年：2016
• 卷：235
• 期：Complete
• 页码：1-13
• 全文大小：3382 K

文摘

Conventional enhanced permeation and retention (EPR) mediates the effects of many drugs, including the accumulation of nanocarriers at tumor sites, but its efficiency remains low. In this study, this limitation was overcome by developing a dual-targeting delivery system based on hyaluronan (HA, a major ligand of CD44) and tetraiodothyroacetic acid (tetrac, a specific ligand of α_vβ₃), which was exploited to carry docetaxel (DTX) for the synergistic active targeting to tumors. First, a tetrac-HA (TeHA) conjugate was synthesized and grafted onto the surfaces of solid lipid nanoparticles (SLNs) (TeHA-SLNs/DTX), with a high encapsulation efficiency of > 91.6%. The resulting SLNs exhibited an approximately toroid morphology revealed using TEM. The cellular uptake and cytotoxicity of various formulations on CD44/α_vβ₃-enriched B16F10 cells were then assessed, and both results confirmed the selective uptake and high cytotoxicity of the TeHA-SLNs/DTX in a TeHA-dependent manner. In vivo imaging and vessel distribution tests revealed the efficiency of synergistic active targeting was higher than that of EPR-mediated passive targeting by the TeHA-SLNs to α_vβ₃-expressing tumor blood vessels and CD44-expressing tumor cells via selective targeting. Finally, in both xenograft tumor mice and in situ lung metastasis tumor mice, tumor growth was significantly inhibited by TeHA-SLNs/DTX. Therefore, TeHA-SLNs are an efficient system for the dual-targeted delivery of drugs to treat cancer in vivo.