期刊
BIOMATERIALS SCIENCE
卷 8, 期 7, 页码 1885-1896出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c9bm01927h
关键词
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资金
- National Science and Technology Major Project of the Ministry of Science and Technology of China [2018ZX10301402]
- National Natural Science Foundation of China [51973243]
- International Cooperation and Exchange of the National Natural Science Foundation of China [51820105004]
- Guangdong Innovative and Entrepreneurial Research Team Program [2016ZT06S029, 2013S086]
- Science and Technology Planning Project of Shenzhen City [JCYJ20170307141438157]
- National Natural Science Foundation of Guangdong Province, China [2017A030313818, 2018A030313033, 81870127]
- Sanming Project of Medicine in Shenzhen [SZSM201911004]
In order to improve active tumor targeting, tumor cell uptake efficiency and circulation time of doxorubicin (DOX) in vivo, we constructed a cleavable PEGylated hyaluronic acid nano-drug delivery system (HA-mPEG(2k)-DOX) based on a tumor microenvironment pH-responsive imine bond. In this study, HA-mPEG(2k)-DOX can self-assemble into stable nanoparticles (HA-mPEG(2k)-DOX NPs) with a particle size of 50 nm. And the NPs can efficiently target CD44 positive CT26 cells and the pH-responsive cleavable PEG shell can be detached under weakly acidic environments and effectively promote the cellular uptake of HA-DOX NPs. Compared with DOX center dot HCl, the HA-mPEG(2k)-DOX NPs can significantly increase the DOX circulation time by 12.5 times, efficiently target the tumor tissues of CT26 tumor-bearing mice and remain for 72 hours. Therefore, the antitumor results in vivo indicated that the HA-mPEG(2k)-DOX NPs have the best anti-tumor effect while reducing the toxicity of the DOX. Overall, the cleavable PEGylated HA-mPEG(2k)-DOX NPs responding to pH-sensitive imine bonds, while actively targeting CD44-positive tumor cells, improve the dilemma of cellular uptake and delivery by the PEGylated nano delivery system.
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