A novel delivery vector for targeted delivery of the antiangiogenic drug paclitaxel to angiogenic blood vessels: TLTYTWS-conjugated PEG–PLA nanoparticles
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- 作者：Fei Tan ; Xiao-hui Mo ; Jian Zhao ; Hui Liang…
- 关键词：TLTYTWS peptide ; Nanoparticle drug delivery system ; Angiogenesis ; Melanoma ; Nanomedicine
- 刊名：Journal of Nanoparticle Research
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：19
- 期：2
- 全文大小：
- 刊物类别：Chemistry and Materials Science
- 刊物主题：Nanotechnology; Inorganic Chemistry; Characterization and Evaluation of Materials; Physical Chemistry; Optics, Lasers, Photonics, Optical Devices;
- 出版者：Springer Netherlands
- ISSN：1572-896X
- 卷排序：19
文摘
Antiangiogenesis has been widely accepted as an attractive strategy to combat tumor growth, invasion, and metastasis. An actively targeting nanoparticle-based drug delivery system (nano-DDS) would provide an alternative method to achieve antiangiogenic antitumor therapy. In the present study, our group fabricated novel nano-DDS, TLTYTWS (TS) peptide-modified poly(ethylene glycol)–poly(lactic acid) (PEG–PLA) nanoparticles (TS-NPs) encapsulating a drug with antiangiogenic potential, paclitaxel (Ptx) (TS-Ptx-NPs). The nanoparticles were uniformly spherical and had a unimodal particle size distribution and slightly negative zeta potential. TS-NPs accumulated significantly in human umbilical vein endothelial cells (HUVECs) via energy-dependent and caveolae- and lipid raft-mediated endocytosis and improved the antiproliferative, antimigratory, and antitube-forming abilities of paclitaxel in vitro. Following intravenous administration, TS-Ptx-NPs presented favorable pharmacokinetic profiles. Melanoma distribution assays confirmed that TS-NPs achieved higher accumulation and penetration at melanoma sites. These results collectively indicated that TLTYTWS-decorated nanoparticles can be considered to be a promising nano-DDS for chemotherapies targeting tumor angiogenesis and have great potential to improve the efficacy of antiangiogenic therapy in melanoma tumor-bearing nude mice.