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

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

  • J Control Release. 2024 Nov:375:422-437. doi: 10.1016/j.jconrel.2024.09.018.
Hongxin Tan 1,  Ziqi Shen 2,  Xiaohua Wang 3,  Sicheng Shu 1,  Jie Deng 1,  Li Lu 2,  Ziyan Fan 2,  Danni Hu 2,  Pu Cheng 4,  Xi Cao 5,  Qi Huang 6
Affiliations

Affiliations

  • 1 Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
  • 2 School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China.
  • 3 Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
  • 4 Department of Gynaecology, The Second Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address: drchengpu@zju.edu.cn.
  • 5 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.
  • 6 Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. Electronic address: huangqi214@163.com.
PMID: 39278355 DOI: 10.1016/j.jconrel.2024.09.018
Abstract

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.

Keywords

Biomimetic nanoparticles; Cell apoptosis; Colorectal cancer; Endoplasmic reticulum-targeted; Ferroptosis.

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