1. Synergistic active targeting of dually integrin αvβ3/CD44-targeted nanoparticles to B16F10 tumors located at different sites of mouse bodies.
- Author
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Shi S, Zhou M, Li X, Hu M, Li C, Li M, Sheng F, Li Z, Wu G, Luo M, Cui H, Li Z, Fu R, Xiang M, Xu J, Zhang Q, and Lu L
- Subjects
- Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents therapeutic use, Apoptosis drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Docetaxel, Drug Liberation, Female, Humans, Hyaluronic Acid chemistry, MCF-7 Cells, Mice, Inbred C57BL, Nanoparticles chemistry, Neoplasms metabolism, Neoplasms pathology, Taxoids chemistry, Taxoids pharmacokinetics, Taxoids therapeutic use, Thyroxine analogs & derivatives, Thyroxine chemistry, Tumor Burden drug effects, Xenograft Model Antitumor Assays, Antineoplastic Agents administration & dosage, Hyaluronan Receptors metabolism, Integrin alphaVbeta3 metabolism, Nanoparticles administration & dosage, Neoplasms drug therapy, Taxoids administration & dosage
- 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., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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