Growth inhibition of pancreatic cancer by targeted delivery of gemcitabine via fucoidan-coated pH-sensitive liposomes

  • Int J Biol Macromol. 2024 Aug 5;277(Pt 3):134517. doi: 10.1016/j.ijbiomac.2024.134517.
Zhenjiang Zheng  1 ,  Mengfei Li  2 ,  Jianchen Yang  3 ,  Xintao Zhou  2 ,  Yonghua Chen  1 ,  Epiphane K Silli  2 ,  Jiali Tang  2 ,  Songlin Gong  1 ,  Yuan Yuan  1 ,  Yihao Zong  4 ,  Jianping Kong  5 ,  Pu Chen  5 ,  Lingxi Yu  5 ,  Shujun Luo  5 ,  Ying Wang  6 ,  Chunlu Tan  7
Affiliations
  • 1. Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • 2. School of Life Sciences and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
  • 3. Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
  • 4. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
  • 5. School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
  • 6. School of Life Sciences and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, China. Electronic address: [email protected].
  • 7. Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: [email protected].
PMID: 39111497 DOI: 10.1016/j.ijbiomac.2024.134517
Abstract

Fucoidan-coated pH sensitive liposomes were designed for targeted delivery of gemcitabine (FU-GEM PSL) to treat pancreatic Cancer (PC). FU-GEM PSL had a particle size of 175.3 ± 4.9 nm, zeta potential of -19.0 ± 3.7 mV, encapsulation efficiency (EE) of 74.05 ± 0.17 %, and drug loading (DL) of 21.27 ± 0.05 %. Cell experiments in vitro showed that FU-GEM PSL could increase the release of GEM and drug concentration, and could inhibit tumor cell proliferation by affecting the cell cycle. FU-GEM PSL entered cells through macropinocytosis and caveolin-mediated endocytosis to exert effects. Meanwhile, the expression of P-selectin was detected in human tissues, demonstrating the feasibility of targeting FU. Moreover, combined with animal experiments in vivo, FU-GEM PSL could inhibit the development of PC. Furthermore, anti-tumor experiments in vivo carried on BALB/c mice indicated that FU-GEM PSL had tumor suppression abilities and safety. Therefore, FU-GEM PSL is a promising formulation for PC therapy.

Keywords
Fucoidan; PH-sensitive liposomes; Pancreatic cancer; Targeting drug delivery.
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