期刊
BIOMATERIALS
卷 69, 期 -, 页码 1-11出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.07.048
关键词
Polymeric nanoparticles; Self-assembly; PEGylation; Biological behaviors; Drug delivery; Cancer therapy
资金
- Core Facility Center for Life Sciences, University of Science and Technology of China
- National Basic Research Program of China (973 Programs) [2012CB932500, 2015CB932100, 2013CB933900]
- National Natural Science Foundation of China [51125012, 51390482]
- Fundamental Research Funds for the Central Universities
Poly(ethylene glycol) (PEG) is usually used to protect nanoparticles from rapid clearance in blood. The effects are highly dependent on the surface PEG density of nanoparticles. However, there lacks a detailed and informative study in PEG density and in vivo drug delivery due to the critical techniques to precisely control the surface PEG density when maintaining other nano-properties. Here, we regulated the polymeric nanoparticles' size and surface PEG density by incorporating poly(E-caprolactone) (PCL) homopolymer into poly(ethylene glycol)-block-poly(E-caprolactone) (PEG-PCL) and adjusting the mass ratio of PCL to PEG-PCL during the nanoparticles preparation. We further developed a library of polymeric nanoparticles with different but controllable sizes and surface PEG densities by changing the molecular weight of the PCL block in PEG-PCL and tuning the molar ratio of repeating units of PCL (CL) to that of PEG (EG). We thus obtained a group of nanoparticles with variable surface PEG densities but with other nano-properties identical, and investigated the effects of surface PEG densities on the biological behaviors of nanoparticles in mice. We found that, high surface PEG density made the nanoparticles resistant to absorption of serum protein and uptake by macrophages, leading to a greater accumulation of nanoparticles in tumor tissue, which recuperated the defects of decreased internalization by tumor cells, resulting in superior antitumor efficacy when carrying docetaxel. (C) 2015 Elsevier Ltd. All rights reserved.
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