2. Academic Validation
  3. Fibrotic collagen-targeted delivery system blocks pancreatic intercellular crosstalk to alleviate pancreatic fibrosis

Fibrotic collagen-targeted delivery system blocks pancreatic intercellular crosstalk to alleviate pancreatic fibrosis

  • J Control Release. 2025 Oct 6;388(Pt 1):114278. doi: 10.1016/j.jconrel.2025.114278.
Hui Wang 1,  Liang Qi 1,  Yue-Fei Fang 2,  Yang Liu 2,  Zheng Ye 3,  Bi-Te Chen 2,  Yi Wang 4,  Hu-Lin Jiang 5,  Ling Li 6
Affiliations

Affiliations

  • 1 Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
  • 2 State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
  • 3 Institute of Computational Science and Technology, Guangzhou University, Guangzhou, Guangdong 510006, China.
  • 4 State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China. Electronic address: wangyi@cpu.edu.cn.
  • 5 State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China; Joint International Research Laboratory of Target Discovery and New Drug Innovation, MOE, China Pharmaceutical University, Nanjing 210009, China; Department of Cardiology and Hypertension Yanbian University Hospital, Yanji 133000, China; College of Pharmacy, Yanbian University, Yanji 133002, China; Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, South Korea. Electronic address: jianghulin3@gmail.com.
  • 6 Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China; Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing 210009, China. Electronic address: lingli@seu.edu.cn.
PMID: 41045968 DOI: 10.1016/j.jconrel.2025.114278
Abstract

Pancreatic fibrosis (PF) is a significant disruption of homeostasis in the pancreas, primarily characterized by excessive extracellular matrix (ECM) deposition due to pancreatic acinar cell (PAC) injury, pancreatic stellate cell (PSC) activation, and persistent inflammatory response. As a hallmark feature of both chronic pancreatitis and pancreatic Cancer, progressive fibrosis exacerbates disease severity and poses significant clinical challenges. Notably, the self-amplifying crosstalk between activated PSCs and injured PACs perpetuates fibrogenesis and undermines therapeutic efficacy. However, currently, no effective strategy is available to modulate intercellular and alleviate pancreatic fibrosis. Herein, we developed dual drug-loaded lipid nanoparticles (JM-CCs) functionalized with a collagen-binding peptide (CBP) and collagenase I on their surface. This design facilitates targeted drug delivery by enabling penetration through the dense ECM barrier to the core of fibrotic lesions. The released melatonin alleviates oxidative stress in PACs, thereby reducing their fibrogenic stimulation of PSCs. Concurrently, the encapsulated JTE013 suppresses PSC activation by modulating Autophagy, leading to decreased ECM production and mitigation of PAC injury. In a caerulein-induced PF mouse model, JM-CCs effectively reduce ECM deposition and repair pancreatic exocrine function. This study provides a novel strategy for regaining pancreatic tissue homeostasis and offers a promising approach for therapies of fibrosis and pancreatic disease.

Keywords

Cellular crosstalk; Collagen targeting; Fibrosis; Lipid nanoparticles; Pancreatic acinar cell; Pancreatic stellate cell.

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