PMID- 31545587 OWN - NLM STAT- MEDLINE DCOM- 20200907 LR - 20211204 IS - 1936-086X (Electronic) IS - 1936-0851 (Linking) VI - 13 IP - 11 DP - 2019 Nov 26 TI - Reshaping Prostate Tumor Microenvironment To Suppress Metastasis via Cancer-Associated Fibroblast Inactivation with Peptide-Assembly-Based Nanosystem. PG - 12357-12371 LID - 10.1021/acsnano.9b04857 [doi] AB - Prostate cancer is one of the most common malignant tumors in men, and inhibiting metastasis is a key event but still a major challenge in prostate cancer treatment. Cancer-associated fibroblasts (CAFs) play an important role in prostate tumor metastasis by shaping the malignant tumor microenvironment. Herein, we constructed a CAF-targeting siRNA delivery system by loading the fibroblast activation protein-alpha (FAP-alpha) antibody onto the cell-penetrating peptide (CPP)-based nanoparticles, which specifically downregulated C-X-C motif chemokine ligand 12 (CXCL12) expression in CAFs. This regulation generated a series of changes through inactivating CAFs so that the malignant prostate tumor microenvironment was reshaped. The tumor cell invasion, migration, and tumor angiogenesis were significantly inhibited, which all contributed to the suppression of the metastasis of an orthotopic prostate tumor. This tumor microenvironment reshaping strategy via CAF targeting and inactivation provides an alternative approach for malignant prostate tumor metastasis inhibition. FAU - Lang, Jiayan AU - Lang J AD - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China. AD - Center of Materials Science and Optoelectronics Engineering , University of Chinese Academy of Sciences , Beijing 100049 , China. AD - Sino-Danish Center for Education and Research , Sino-Danish College of UCAS , Beijing 100190 , China. FAU - Zhao, Xiao AU - Zhao X AD - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China. AD - Center of Materials Science and Optoelectronics Engineering , University of Chinese Academy of Sciences , Beijing 100049 , China. FAU - Qi, Yingqiu AU - Qi Y AD - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China. AD - School of Basic Medical Sciences , Zhengzhou University , Henan 450001 , China. FAU - Zhang, Yinlong AU - Zhang Y AD - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China. AD - Center of Materials Science and Optoelectronics Engineering , University of Chinese Academy of Sciences , Beijing 100049 , China. FAU - Han, Xuexiang AU - Han X AUID- ORCID: 0000-0003-0011-5222 AD - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China. AD - Center of Materials Science and Optoelectronics Engineering , University of Chinese Academy of Sciences , Beijing 100049 , China. FAU - Ding, Yanping AU - Ding Y AD - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China. AD - Center of Materials Science and Optoelectronics Engineering , University of Chinese Academy of Sciences , Beijing 100049 , China. FAU - Guan, Jiajing AU - Guan J AD - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China. FAU - Ji, Tianjiao AU - Ji T AUID- ORCID: 0000-0002-4479-4821 AD - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China. AD - Center of Materials Science and Optoelectronics Engineering , University of Chinese Academy of Sciences , Beijing 100049 , China. FAU - Zhao, Ying AU - Zhao Y AD - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China. AD - Center of Materials Science and Optoelectronics Engineering , University of Chinese Academy of Sciences , Beijing 100049 , China. FAU - Nie, Guangjun AU - Nie G AUID- ORCID: 0000-0001-5040-9793 AD - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China. AD - Center of Materials Science and Optoelectronics Engineering , University of Chinese Academy of Sciences , Beijing 100049 , China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190930 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - 0 (Cell-Penetrating Peptides) RN - 0 (Chemokine CXCL12) RN - 0 (Membrane Proteins) RN - 0 (RNA, Small Interfering) RN - EC 3.4.- (Endopeptidases) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 3.4.21.- (fibroblast activation protein alpha) RN - EC 3.4.24.- (Gelatinases) SB - IM MH - Animals MH - *Cancer-Associated Fibroblasts/drug effects/metabolism MH - Cell-Penetrating Peptides/chemistry/pharmacology MH - Chemokine CXCL12/genetics/metabolism MH - Endopeptidases MH - Gelatinases/antagonists & inhibitors/metabolism MH - Gene Silencing MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Male MH - Membrane Proteins/antagonists & inhibitors/metabolism MH - Mice, Inbred BALB C MH - Mice, Nude MH - Nanomedicine/*methods MH - Nanoparticles/chemistry MH - Neoplasm Metastasis/prevention & control MH - PC-3 Cells MH - *Prostatic Neoplasms/metabolism/pathology MH - RNA, Small Interfering MH - Serine Endopeptidases/metabolism MH - *Tumor Microenvironment/drug effects/physiology OTO - NOTNLM OT - CXCL12 gene silencing OT - cancer-associated fibroblast inactivation OT - metastasis inhibition OT - peptide assembly OT - prostate cancer EDAT- 2019/09/24 06:00 MHDA- 2020/09/08 06:00 CRDT- 2019/09/24 06:00 PHST- 2019/09/24 06:00 [pubmed] PHST- 2020/09/08 06:00 [medline] PHST- 2019/09/24 06:00 [entrez] AID - 10.1021/acsnano.9b04857 [doi] PST - ppublish SO - ACS Nano. 2019 Nov 26;13(11):12357-12371. doi: 10.1021/acsnano.9b04857. Epub 2019 Sep 30.