2. Academic Validation
  3. CXCL12-targeting siRNA nanoparticles alleviate immunosuppression and inhibit tumor progression in esophageal squamous cell carcinoma

CXCL12-targeting siRNA nanoparticles alleviate immunosuppression and inhibit tumor progression in esophageal squamous cell carcinoma

  • J Nanobiotechnology. 2025 Jul 16;23(1):519. doi: 10.1186/s12951-025-03476-x.
Shuyao Zhang # 1,  Hong Jiang # 2,  Chengkuan Zhao # 3,  Yanli Lei # 4,  Shaojie Liu # 5,  Chengcheng Xu 1,  Xiaoshan Chen 1,  Danling Zheng 1,  Xiaolong Wu 3,  Xinyue Lin 6,  Wang Chen 1,  Yun Chen 1,  Jianxiang Huang 3,  XiaoLong Wei 7,  Yihui Huang 8,  Chaoxian Lin 9 10
Affiliations

Affiliations

  • 1 Department of Pharmacy, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, 510220, People's Republic of China.
  • 2 Department of Nursing, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, 510220, People's Republic of China.
  • 3 College of Pharmacy, Jinan University, Guangzhou, 510220, People's Republic of China.
  • 4 Department of Pharmacy, The 2nd, People's Hospital of Bijie, Bijie, 551700, Guizhou, People's Republic of China.
  • 5 Department of Gastrointestinal Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, 510220, People's Republic of China.
  • 6 Department of Pharmacology, Shantou University Medical College, Shantou, 515041, Guangdong, People's Republic of China.
  • 7 Department of Pathology, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, 515041, People's Republic of China. weixiaolonghh@126.com.
  • 8 Department of Pediatrics, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, 510220, Guangdong Province, People's Republic of China. hyh930@sina.com.
  • 9 Department of Pharmacology, Shantou University Medical College, Shantou, 515041, Guangdong, People's Republic of China. cxlin@stu.edu.cn.
  • 10 Department of Pharmacy, Shantou Chaonan Minsheng Hospital, Shantou, 515000, Guangdong Province, People's Republic of China. cxlin@stu.edu.cn.
  • # Contributed equally.
PMID: 40671009 DOI: 10.1186/s12951-025-03476-x
Abstract

Esophageal squamous cell carcinoma (ESCC) is associated with a highly immunosuppressive tumor microenvironment (TME), driven in part by cancer-associated fibroblasts (CAFs) that promote immune evasion through the secretion of CXCL12. CXCL12 interacts with the CXCR4 receptor on immune cells, disrupting CD8+ T cell migration and anti-tumor function. To address this, we developed an innovative siRNA-based therapeutic approach targeting CXCL12 in CAFs. Using lipid nanocarriers (LNCs) as delivery vehicles, we engineered LNCs@si-CXCL12 nanoparticles to specifically silence CXCL12 expression in CAFs. In vitro studies demonstrated that LNCs@si-CXCL12 restored CD8+ T cell migration and inhibited ESCC cell proliferation and migration. In vivo experiments in a spontaneous ESCC mouse model showed that CXCL12 silencing through nanoparticle delivery significantly reduced tumor growth, enhanced CD8+ T cell-mediated tumoricidal activity, and improved overall survival. These findings highlight the potential of siRNA-loaded nanoparticles targeting CXCL12 as a novel therapeutic strategy to reprogram the immunosuppressive TME and enhance immune responses in ESCC. This approach provides a promising avenue for improving treatment outcomes and overcoming immune evasion in ESCC.

Keywords

CXCL12; Cancer-associated fibroblasts; Esophageal squamous cell carcinoma; SiRNA nanoparticles; Tumor microenvironment.

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