期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 59, 期 41, 页码 17944-17950出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202006895
关键词
chemotherapy; drug delivery; gene therapy; nucleoside analogue; self-assembly
资金
- National Key Research and Development Program of China [2018YFC1106100, 2018YFC1106102, 2018YFA0902600]
- National Natural Science Foundation of China [21805129, 21661162001, 21673139, 51973112, 51690151, 81671673, 81871329]
Combinatorial antitumor therapies using different combinations of drugs and genes are emerging as promising ways to overcome drug resistance, which is a major cause for the failure of cancer treatment. However, dramatic pharmacokinetic differences of drugs greatly impede their combined use in cancer therapy, raising the demand for drug delivery systems (DDSs) for tumor treatment. By employing fluorescent dithiomaleimide (DTM) as a linker, we conjugate two paclitaxel (PTX) molecules with a floxuridine (FdU)-integrated antisense oligonucleotide (termed chemogene) to form a drug-chemogene conjugate. This PTX-chemogene conjugate can self-assemble into a spherical nucleic acid (SNA)-like micellular nanoparticle as a carrier-free DDS, which knocks down the expression of P-glycoprotein and subsequently releases FdU and PTX to exert a synergistic antitumor effect and greatly inhibit tumor growth.
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