Doxorubicin-conjugated Escherichia coli Nissle 1917 swimmers to achieve tumor targeting and responsive drug release

Journal of Controlled Release : Official Journal of the Controlled Release Society
Songzhi XieXiaohong Li

Abstract

The use of bacteria as drug carriers meets several challenges, such as biocompatibility, motility deterioration after drug loading and lack of in vivo verification. Escherichia coli Nissle 1917 (EcN) is one of the best studied probiotic strains, and doxorubicin (DOX) is conjugated onto EcN in the current study via acid-labile linkers of cis-aconitic anhydride (EcN-ca-Dox), realizing the bacteria-directed accumulation and acid-responsive release of anticancer drugs in tumors. The drug conjugation has maintained the bacterial motion profiles of over 9μm/s and cell viability of over 70%. After 3h and 3days of intravenous injection of EcN-ca-Dox, DOX accumulations in tumors are determined as 12.9% and 6.4% of the injected doses per gram of tissue, respectively, which are much higher than the commonly used nanocarriers. Compared with free DOX and DOX-conjugated EcN via stable linkers of succinic anhydride, the EcN-ca-Dox treatment improves the antitumor efficacy with respect to the tumor growth inhibition, prolongation of animal survivals, and apoptosis induction of tumor cells. In addition, EcN has been cleaned off from tumors and other tissues after antimicrobial treatment. Thus, the acid-labile EcN conjugates provide a safe and c...Continue Reading

Citations

Mar 11, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Cheng XuRupei Tang
Sep 23, 2020·Micromachines·Elizabeth E NiedertDavid J Cappelleri
Jan 8, 2020·Sensors·Zhiyong SunAinhoa Revilla-Guarinos
Sep 25, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Luisa SonntagVeronika Magdanz
Jan 29, 2021·International Journal of Pharmaceutics·Jianting ZhangAi-Zheng Chen
Nov 7, 2020·Advanced Materials Interfaces·Víctor M MorenoMaría Vallet-Regí
Jun 18, 2021·Advanced Drug Delivery Reviews·Xi HuDaishun Ling
Jun 14, 2021·Seminars in Cancer Biology·Muhammad Jameel Mughal, Hang Fai Kwok
Nov 17, 2021·Analytical Chemistry·Tianyu JiangYouming Zhang

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