2. Academic Validation
  3. Chemo-photothermal nanoplatform with diselenide as the key for ferroptosis in colorectal cancer

Chemo-photothermal nanoplatform with diselenide as the key for ferroptosis in colorectal cancer

  • J Control Release. 2024 Jan 17:366:684-693. doi: 10.1016/j.jconrel.2024.01.024.
Kaili Deng 1,  Hailong Tian 2,  Tingting Zhang 2,  Yajie Gao 1,  Edouard C Nice 3,  Canhua Huang 4,  Na Xie 5,  Guoliang Ye 6,  Yuping Zhou 7
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315020, China.
  • 2 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
  • 3 Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
  • 4 The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315020, China; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
  • 5 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China. Electronic address: naxie@scu.edu.cn.
  • 6 The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315020, China. Electronic address: ndfyygl@163.com.
  • 7 The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315020, China. Electronic address: fyzhouyuping@nbu.edu.cn.
PMID: 38224739 DOI: 10.1016/j.jconrel.2024.01.024
Abstract

Colorectal Cancer (CRC) is a prevalent clinical malignancy of the gastrointestinal system, and its clinical drug resistance is the leading cause of poor prognosis. Mechanistically, CRC cells possess a specific oxidative stress defense mechanism composed of a significant number of endogenous antioxidants, such as glutathione, to combat the damage produced by drug-induced excessive Reactive Oxygen Species (ROS). We report on a new anti-CRC nanoplatform, a multifunctional chemo-photothermal nanoplatform based on Camptothecin (CPT) and IR820, an indocyanine dye. The implementation of a GSH-triggered ferroptosis-integrated tumor chemo-photothermal nanoplatform successfully addressed the poor targeting ability of CPT and IR820 while exhibiting significant growth inhibitory effects on CRC cells. Mechanistically, to offset the oxidative stress created by the broken SeSe bonds, endogenous GSH was continuously depleted, which inactivated GPX4 to accumulate lipid peroxides and induce Ferroptosis. Concurrently, exogenously administered linoleic acid was oxidized under photothermal conditions, resulting in an increase in LPO accumulation. With the breakdown of the oxidative stress defense system, chemotherapeutic efficacy could be effectively enhanced. In combination with photoacoustic imaging, the nanoplatform could eradicate solid tumors by means of ferroptosis-sensitized chemotherapy. This study indicates that chemotherapy involving a Ferroptosis mechanism is a viable method for the treatment of CRC.

Keywords

Chemo-phototherapy; Colorectal cancer; Ferroptosis; Se-Se bonds.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z