Citation: Han Han, Bi-Te Chen, Jia-Rong Ding, Jin-Ming Si, Tian-Jiao Zhou, Yi Wang, Lei Xing, Hu-Lin Jiang. A PDGFRβ-targeting nanodrill system for pancreatic fibrosis therapy[J]. Chinese Chemical Letters, ;2024, 35(10): 109583. doi: 10.1016/j.cclet.2024.109583 shu

A PDGFRβ-targeting nanodrill system for pancreatic fibrosis therapy

Han Han ^{a, 1} ,
Bi-Te Chen ^{a, 1} ,
Jia-Rong Ding ^{c, 1} ,
Jin-Ming Si ^a ,
Tian-Jiao Zhou ^a ,
Yi Wang ^a ,
Lei Xing ^{a, *,} ,
Hu-Lin Jiang ^{a, b, *,}

a.
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China
b.
College of Pharmacy, Yanbian University, Yanji 133002, China
c.
Department of Nephrology, Changhai Hospital, Naval Medical University, Shanghai 200433, China

xinglei6xl@163.com

jianghulin3@163.com

Received Date: 29 November 2023
Revised Date: 12 January 2024
Accepted Date: 21 January 2024
Available Online: 1 February 2024

Figures(5)

Activated pancreatic stellate cells (PSCs) are the main source of collagen layer deposition and the key target in pancreatic fibrosis. However, no effective treatment specific to pancreatic fibrosis clinically, owing to the drug accumulation blocked by the collagen barrier and thus it is difficult to inhibit activated PSCs precisely. Herein, a PSCs-targeting nano-system based on “nanodrill” strategy (LA-PC) was designed to enhance the accumulation of all-trans retinoic acid (ATRA) in PSCs, relying on the platelet-derived growth factor receptor beta (PDGFRβ)-targeting peptide (pPB: C*SRNLIDC*) and collagenase (Col). After being injected into fibrotic mice via tail vein, the Col modified on LA-PC can remove the excess collagen layer, and the drug delivery efficiency through pPB targeting peptide was more than 5 times higher than that of free ATRA, as well as the degree of fibrosis significantly reduced. Notably, this nano-system effectively inhibited platelet-derived growth factor subunit B (PDGF-BB)/PDGFRβ axis on PSCs via a down-regulated extracellular signal-regulated protein kinase (ERK) pathway, and accordingly reduced the level of PDGF-BB. Thus, the smart platform provided a promising strategy for the treatment of pancreatic fibrosis to achieve the precise regulation of PSCs.
- Pancreatic fibrosis,
- Pancreatic stellate cells,
- Liposome,
- PDGFRβ,
- pPB peptide
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