期刊
NANO LETTERS
卷 22, 期 24, 页码 10040-10048出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.2c03763
关键词
phenolic acid derivative; human serum albumin; nanocomplex; cancer
类别
资金
- National Natural Science Foundation of China [82273878]
- Science and Technology Innovation Projects for Young and Middleaged Talents of Shenyang [RC200406]
Inspired by natural phenolic-protein interactions, the study developed an albumin-bound technology based on phenolic acid derivatives. These derivatives can bind to albumin and form nanocomplexes. The technology has been successfully applied to various anticancer drugs and showed promising results in breast cancer models.
Inspired by the natural phenomenon of phenolic-protein interactions, we translate this naturally evolved interaction to a phenolic acid derivative based albumin bound technology, through the synthesis of phenolic acid derivatives comprising a therapeutic cargo linked to a phenolic motif. Phenolic acid derivatives can bind to albumin and form nanocomplexes after microfluidic mixing. This strategy has been successfully applied to different types of anticancer drugs, including taxanes, anthraquinones, etoposides, and terpenoids. Paclitaxel was selected as a model drug for an in-depth study. Three novel paclitaxel-phenolic acid conjugates have been synthesized. Molecular dynamics simulations provide insights into the self-assembled mechanisms of phenolic-protein nanocomplexes. The nanocomplexes show improved pharmacokinetics, elevated tolerability, decreased neurotoxicity, and enhanced anticancer efficacies in multiple murine xenograft models of breast cancer, in comparison with two clinically approved formulations, Taxol (polyoxyethylated castor oil-formulated paclitaxel) and Abraxane (nab-paclitaxel). Such a robust system provides a broadly applicable platform for the development of albumin-based nanomedicines and has great potential for clinical translation.
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