期刊
BIOMATERIALS
卷 33, 期 6, 页码 1948-1958出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.11.051
关键词
Biodegradable copolymers; Cancer nanotechnology; Chemotherapeutic engineering; Drug targeting; Nanomedicine; Herceptin (R)
资金
- Agency of Science, Technology and Research (A*STAR), Singapore (SERC) [102-145-0118]
- National University of Singapore
There have been two strategies developed in the recent literature for quantitative control of the targeting effects for drug delivery by ligand-conjugated nanoparticles of biodegradable copolymer blend such as PLGA/PLGA-PEG, i.e. the pre-conjugation strategy and the post-conjugation strategy, in which the ligand conjugation was made before and after the nanoparticle formulation respectively. This research developed another drug delivery system of the PLA-TPGS/TPGS-COOH copolymer blend and further improved the post-conjugation strategy to precisely control the targeting effects by two ways: one is to adjust the PIA-TPGS:TPGS-COOH copolymer blend ratio in the nanoparticle formulation process, which provides a way for coarse control, and another is to control the feeding concentration of the ligand in the herceptin conjugation process, which further provides a fine control. Herceptin conjugation was visualized by the FETEM with immumogold labeling and further quantified by the two techniques, i.e. the Bradford assay and the flow cytometry to confirm each other. The positive correlation between the surface density of the ligand and the cellular internalization as well as the cytotoxicity of the nanoparticle formulations was assessed, which demonstrated that the strategy developed in this research is simple and feasible, which can precisely control the targeting effects of the nanoparticles of biodegradable polymers as well as other nanocarriers such as micelles and liposomes. (C) 2011 Elsevier Ltd. All rights reserved.
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