期刊
ACS NANO
卷 11, 期 9, 页码 8668-8678出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.7b01026
关键词
peptide-hybrid liposome; MMP-2 responsive; pancreatic stellate cells; down-regulation of ECM; enhanced pancreatic tumor therapy
类别
资金
- MOST 973 [2013CB932701]
- NSFC [81630068, 21373067, 51673051, 31325010, 11621505, 31571021]
- Beijing Nova Program [Z171100001117010]
- Beijing Natural Science Foundation [7172164]
- Beijing Municipal Science and Technology Commission [Z161100000116035]
- Frontier Research Program of Chinese Academy of Sciences [QYZDJ-SSW-SLH022]
- Youth Innovation Promotion Association CAS [2017056]
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.
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