Mitigation of Anti-Drug Antibody Production for Augmenting Anticancer Efficacy of Therapeutic Protein via Co-Injection of Nano-Rapamycin.

Autor: Chang Y; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Xiong W; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.; Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510450, China.; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, 528437, China., Zou C; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China., Zeng P; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China., Hou J; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210023, China., Muhitdinov B; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.; Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences, Tashkent, 100125, Uzbekistan., Shen Y; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China., Huang Y; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, 528437, China.; University of Chinese Academy of Sciences, Beijing, 100049, China., Guo S; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2024 Jan; Vol. 20 (3), pp. e2303916. Date of Electronic Publication: 2023 Sep 13.
DOI: 10.1002/smll.202303916
Abstrakt: The induction of anti-drug antibody (ADA) is a formidable challenge for protein-based therapy. Trichosanthin (TCS) as a class of ribosome-inactivating proteins is widely studied in tumor treatment. However, the immunogenicity can induce the formation of ADA, which can cause hypersensitivity reactions and neutralize the efficacy of TCS, thus limiting its clinical application in cancer therapy. Here, a promising solution to this issue is presented by co-administration of the rapamycin nanoparticles and TCS. PEGylated rapamycin amphiphilic molecule is designed and synthesized as a prodrug and a delivery carrier, which can self-assemble into a nanoparticle system with encapsulation of free rapamycin, a hydrophobic drug. It is found that co-injection of the PEGylated rapamycin nanoparticles and TCS could mitigate the formation of anti-TCS antibody via inducing durable immunological tolerance. Importantly, the combination of TCS and the rapamycin nanoparticles has an enhanced effect on inhibit the growth of breast cancer. This work provides a promising approach for protein toxin-based anticancer therapy and for promoting the clinical translation.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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