title: An MMP-2 Responsive Liposome Integrating Antifibrosis and Chemotherapeutic Drugs for Enhanced Drug Perfusion and Efficacy in Pancreatic Cancer.
abstract: Fibrotic stroma, a critical character of pancreatic tumor microenvironment, provides a critical barrier against the penetration and efficacy of various antitumor drugs. Therefore, new strategies are urgently needed to alleviate the fibrotic mass and increase the drug perfusion within pancreatic cancer tissue. In our current work, we developed a β-cyclodextrin (β-CD) modified matrix metalloproteinase-2 (MMP-2) responsive liposome, integrating antifibrosis and chemotherapeutic drugs for regulation of pancreatic stellate cells (PSCs), a key source of the fibrosis, and targeted delivery of cytotoxic drugs for pancreatic cancer therapy. These liposomes disassembed into two functional parts upon MMP-2 cleavage at the tumor site. One part was constituted by the β-CDs and the antifibrosis drug pirfenidone, which was kept in the stroma and inhibited the expression of collagen I and TGF-β in PSCs, down-regulating the fibrosis and decreasing the stromal barrier. The other segment, the RGD peptide-modified-liposome loading the chemotherapeutic drug gemcitabine, targeted and killed pancreatic tumor cells. This integrated nanomedicine, showing an increased drug perfusion without any overt side effects, may provide a potential strategy for improvement of the pancreatic cancer therapy.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Ji
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Suping
authors.initials: S
authors.lastname: Li
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.|College of Pharmaceutical Science, Jilin University , Changchun 130021, China.
authors.forename: Yinlong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Jiayan
authors.initials: J
authors.lastname: Lang
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pancreatic Carcinoma Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer Key Laboratory of Cancer Prevention and Therapy , Tianjin 300060, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Yiye
authors.initials: Y
authors.lastname: Li
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Pancreatic Carcinoma Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer Key Laboratory of Cancer Prevention and Therapy , Tianjin 300060, China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Hao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Nie
mesh_terms: D016503:Drug Delivery Systems; D065546:Drug Liberation; D005355:Fibrosis / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000627:therapeutic use; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry* / Q000627:therapeutic use; D050997:Nanomedicine; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D058954:Pancreatic Stellate Cells / Q000187:drug effects / Q000473:pathology; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology; D059016:Tumor Microenvironment / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D008081:Liposomes; D047392:beta-Cyclodextrins; D020778:Matrix Metalloproteinase 2; C031215:betadex
keywords: MMP-2 responsive liposome; antifibrosis; enhanced drug perfusion; pancreatic cancer; pancreatic stellate cells