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M1 Macrophage-Derived Extracellular Vesicles Loaded with CX3CR1 siRNA for the Treatment of Pancreatic Cancer

Cheng Miao1,2, Guangzhao Huang1,2, Yi Wen3

  • 1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.

ACS Applied Materials & Interfaces
|July 2, 2025
PubMed

Insights

This study shows M1 macrophage extracellular vesicles loaded with siRNA targeting CX3CR1 effectively inhibit pancreatic cancer growth. This novel gene therapy approach offers a promising strategy for treating pancreatic ductal adenocarcinoma.

Area of Science:

  • Oncology
  • Gene Therapy
  • Nanomedicine

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with limited treatment options.
  • The CX3CL1-CX3CR1 pathway promotes PDAC progression, making it a therapeutic target.
  • Gene therapy using small interfering RNA (siRNA) presents a potential strategy for PDAC treatment.

Purpose of the Study:

  • To investigate the therapeutic potential of siRNA targeting CX3CR1 (siCX3CR1) delivered via M1 macrophage-derived extracellular vesicles (M1 EVs) for PDAC.
  • To evaluate the efficacy of M1 EV/siCX3CR1 in inhibiting PDAC cell proliferation and migration in vitro and tumor growth in vivo.

Main Methods:

  • siCX3CR1 was successfully loaded into extracellular vesicles derived from M1 macrophages.
  • In vitro experiments assessed the impact of M1 EV/siCX3CR1 on AsPC-1 pancreatic cancer cell proliferation and migration.
  • In vivo studies utilized an AsPC-1 subcutaneous tumor model to evaluate the tumor-suppressive effect of M1 EV/siCX3CR1.

Main Results:

  • M1 EVs effectively encapsulated siCX3CR1.
  • M1 EV/siCX3CR1 significantly suppressed the proliferation and migration of AsPC-1 cells in vitro.
  • M1 EV/siCX3CR1 demonstrated a significant tumor-suppressive effect in the in vivo PDAC model.

Conclusions:

  • Loading siCX3CR1 into M1 EVs is a feasible and effective strategy for PDAC treatment.
  • This M1 EV-based gene therapy approach shows significant therapeutic promise for pancreatic cancer.
Keywords:
CX3CR1M1 macrophagesextracellular vesiclespancreatic ductal adenocarcinomasmall interfering RNA

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