Carrier-Free Delivery of Precise Drug-Chemogene Conjugates for Synergistic Treatment of Drug-Resistant Cancer.

Abstract

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.

• Authors: Lijuan Zhu, Yuanyuan Guo, Qiuhui Qian, Deyue Yan, Yuehua Li, Xinyuan Zhu, Chuan Zhang
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 59 Issue 41 Pg. 17944-17950 (10 05 2020) ISSN: 1521-3773 [Electronic] Germany
• PMID: 32643224 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Wiley-VCH GmbH.

Chemical References

• Antineoplastic Agents

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Drug Resistance, Neoplasm (drug effects)
• HeLa Cells
• Humans
• Mice
• Microscopy, Atomic Force
• Microscopy, Electron, Transmission
• Neoplasms (drug therapy)