Designing Liposomes to Suppress Extracellular Matrix Expression to Enhance Drug Penetration and Pancreatic Tumor Therapy

Tianjiao Ji, Jiayan Lang, Jing Wang, Rong Cai, Yinlong Zhang, Feifei Qi, Lijing Zhang, Xiao Zhao, Wenjing Wu, Jihui Hao, Zhihai Qin, Ying Zhao, Guangjun Nie

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

During pancreatic tumor development, pancreatic stellate cells (PSCs) proliferate exuberantly to secrete extracellular matrix (ECM) in the tumor stroma, which presents major barriers for drug delivery and penetration in tumor tissue. Thus, down-regulating ECM levels via regulation of the PSCs may allow enhanced penetration of therapeutic drugs and thereby enhancing their therapeutic efficacy. To regulate the PSCs, a matrix metalloproteinase-2 (MMP-2) responsive peptide-hybrid liposome (MRPL) was constructed via coassembly of a tailor-designed MMP-2 responsive amphiphilic peptide and phospholipids. By utilizing the MMP-2-rich pathological environment, the pirfenidone (PFD) loaded MRPL (MRPL-PFD) can specifically release PFD at the pancreatic tumor site and down-regulate the multiple components of ECM expressed by the PSCs. This resulted in a significant increase in the penetration of gemcitabine into the tumor tissue and enhanced the efficacy of gemcitabine for pancreatic tumor. Our design tailored for antifibrosis of pancreatic cancer may provide a practical approach to build functional liposomes through supramolecular assembly, and regulation of ECM may be a promising adjuvant therapeutic strategy for pancreatic and other ECM-rich tumors.

Original languageEnglish (US)
Pages (from-to)8668-8678
Number of pages11
JournalACS Nano
Volume11
Issue number9
DOIs
StatePublished - Sep 26 2017

Keywords

  • MMP-2 responsive
  • down-regulation of ECM
  • enhanced pancreatic tumor therapy
  • pancreatic stellate cells
  • peptide-hybrid liposome

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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