Endoplasmic reticulum-targeted biomimetic nanoparticles induce apoptosis and ferroptosis by regulating endoplasmic reticulum function in colon cancer.

Autor: Tan H; Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China., Shen Z; School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China., Wang X; Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China., Shu S; Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China., Deng J; Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China., Lu L; School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China., Fan Z; School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China., Hu D; School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China., Cheng P; Department of Gynaecology, The Second Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address: drchengpu@zju.edu.cn., Cao X; School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China; Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. Electronic address: caoxi@ahmu.edu.cn., Huang Q; Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. Electronic address: huangqi214@163.com.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Nov; Vol. 375, pp. 422-437. Date of Electronic Publication: 2024 Sep 19.
DOI: 10.1016/j.jconrel.2024.09.018
Abstrakt: Colorectal cancer (CRC) is a major threat to human health, as it is one of the most common malignancies with a high incidence and mortality rate. The cancer cell membrane (CCM) has significant potential in targeted tumor drug delivery due to its membrane antigen-mediated homologous targeting ability. The endoplasmic reticulum (ER) in cancer cells plays a crucial role in apoptosis and ferroptosis. In this study, we developed an ER-targeted peptide-modified CCM-biomimetic nanoparticle-delivered lovastatin (LOV) nanomedicine delivery system (EMPP-LOV) for cancer treatment. Both in vitro and in vivo experiments demonstrated that EMPP could effectively target cancer cells and localize within the ER. EMPP-LOV modulated ER function to promote apoptosis and ferroptosis in tumor cells. Furthermore, synergistic antitumor efficacy was observed in both in vitro and in vivo models. EMPP-LOV induced apoptosis in CRC cells by over-activating endoplasmic reticulum stress and promoted ferroptosis by inhibiting the mevalonate pathway, leading to synergistic tumor growth inhibition with minimal toxicity to major organs. Overall, the EMPP-LOV delivery system, with its subcellular targeting capability within tumor cells, presents a promising therapeutic platform for CRC treatment.
Competing Interests: Declaration of competing interest The authors declare no competing financial interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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