期刊
BIOMACROMOLECULES
卷 22, 期 10, 页码 4169-4180出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.1c00662
关键词
-
资金
- Norway Grants 2014-2021 via the National Centre for Research and Development [NOR/POLNOR/DUALDRUG/0058/2019-00]
Despite being the second leading cause of death worldwide, cancer still lacks a fully effective therapy, highlighting the urgent need for new targeted anticancer drugs. Researchers have developed novel protein-drug conjugates that successfully inhibit tumor growth in a mouse model of human breast cancer.
Worldwide, cancer is the second leading cause of death. Regardless of the continuous progress in medicine, we still do not have a fully effective anti-cancer therapy. Therefore, the search for new targeted anticancer drugs is still an unmet need. Here, we present novel protein-drug conjugates that inhibit tumor growth in a mouse model of human breast cancer. We developed conjugates based on fibroblast growth factor (FGF2) with improved biophysical and biological properties for the efficient killing of cancer cells overproducing fibroblast growth factor receptor 1 (FGFR1). We used hydrophilic and biocompatible PEG4 or PEG27 molecules as a spacer between FGF2 and the toxic agent monomethyl auristatin E. All conjugates exhibited a cytotoxic effect on FGFR1-positive cancer cell lines. The conjugate with the highest hydrodynamic size (42 kDa) and cytotoxicity was found to efficiently inhibit tumor growth in a mouse model of human breast cancer.
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