Doxorubicin-based ENO1 targeted drug delivery strategy enhances therapeutic efficacy against colorectal cancer.

Autor: Liu J; China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, Beijing 100700, China., Hu X; China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, Beijing 100700, China., Yu G; China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, Beijing 100700, China., Wang Q; China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, Beijing 100700, China., Gu L; China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, Beijing 100700, China., Shen J; China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, Beijing 100700, China., Zhao Q; China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, Beijing 100700, China., Sun H; Nanjing Agricultural University, Nanjing 210009, China., Wang S; Nanjing Agricultural University, Nanjing 210009, China., Guo Z; China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, Beijing 100700, China; College of Pharmacy, Henan University of Chinese Medicine, Henan Zhengzhou 450046, China., Zhao Y; China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, Beijing 100700, China. Electronic address: 1989@icmm.ac.cn., Ma H; China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, Beijing 100700, China. Electronic address: hma@icmm.ac.cn.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Jun; Vol. 224, pp. 116220. Date of Electronic Publication: 2024 Apr 17.
DOI: 10.1016/j.bcp.2024.116220
Abstrakt: Alpha-enolase (ENO1), a multifunctional protein with carcinogenic properties, has emerged as a promising cancer biomarker because of its differential expression in cancer and normal cells. On the basis of this characteristic, we designed a cell-targeting peptide that specifically targets ENO1 and connected it with the drug doxorubicin (DOX) by aldehyde-amine condensation. A surface plasmon resonance (SPR) assay showed that the affinity for ENO1 was stronger (KD = 2.5 µM) for the resulting cell-targeting drug, DOX-P, than for DOX. Moreover, DOX-P exhibited acid-responsive capabilities, enabling precise release at the tumor site under the guidance of the homing peptide and alleviating DOX-induced cardiotoxicity. An efficacy experiment confirmed that, the targeting ability of DOX-P toward ENO1 demonstrated superior antitumor activity against colorectal cancer than that of DOX, while reducing its toxicity to cardiomyocytes. Furthermore, in vivo metabolic distribution results indicated low accumulation of DOX-P in nontumor sites, further validating its targeting ability. These results showed that the ENO1-targeted DOX-P peptide has great potential for application in targeted drug-delivery systems for colorectal cancer therapy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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