1. Synergistic active targeting of dually integrin α v β 3 /CD44-targeted nanoparticles to B16F10 tumors located at different sites of mouse bodies
- Author
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Guo-lin Wu, Xin Li, Chenwen Li, Li Min, Ruoqiu Fu, Li Zhuoheng, Qian Zhang, Min Hu, Fangfang Sheng, Laichun Lu, Huan-huan Cui, Luo Minghe, Min Zhou, Xiang Mingfeng, Xu Jing, Ziwei Li, and Sanjun Shi
- Subjects
0301 basic medicine ,Pharmaceutical Science ,Antineoplastic Agents ,Apoptosis ,Docetaxel ,02 engineering and technology ,03 medical and health sciences ,chemistry.chemical_compound ,In vivo ,Cell Line, Tumor ,Neoplasms ,Solid lipid nanoparticle ,Hyaluronic acid ,Animals ,Humans ,Hyaluronic Acid ,Cytotoxicity ,Cell Proliferation ,Integrin alphaVbeta3 ,biology ,Chemistry ,Cell growth ,CD44 ,021001 nanoscience & nanotechnology ,Xenograft Model Antitumor Assays ,Tumor Burden ,Mice, Inbred C57BL ,body regions ,Drug Liberation ,Thyroxine ,Hyaluronan Receptors ,030104 developmental biology ,Immunology ,MCF-7 Cells ,Cancer research ,biology.protein ,Nanoparticles ,Female ,Taxoids ,Nanocarriers ,0210 nano-technology - Abstract
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 αvβ3), 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/αvβ3-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 αvβ3-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.
- Published
- 2016