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Carrier‐Free Delivery of Precise Drug–Chemogene Conjugates for Synergistic Treatment of Drug‐Resistant Cancer
Author(s) -
Zhu Lijuan,
Guo Yuanyuan,
Qian Qiuhui,
Yan Deyue,
Li Yuehua,
Zhu Xinyuan,
Zhang Chuan
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202006895
Subject(s) - conjugate , paclitaxel , floxuridine , drug , drug delivery , chemistry , linker , pharmacology , drug carrier , nucleic acid , drug resistance , cancer , medicine , biochemistry , biology , fluorouracil , computer science , mathematical analysis , mathematics , organic chemistry , operating system , microbiology and biotechnology
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.