title: Protease-Responsive Prodrug with Aggregation-Induced Emission Probe for Controlled Drug Delivery and Drug Release Tracking in Living Cells.
abstract: Controlled drug delivery and real-time tracking of drug release in cancer cells are essential for cancer therapy. Herein, we report a protease-responsive prodrug (DOX-FCPPs-PyTPE, DFP) with aggregation-induced emission (AIE) characteristics for controlled drug delivery and precise tracking of drug release in living cells. DFP consists of three components: AIE-active tetraphenylethene (TPE) derivative PyTPE, functionalized cell penetrating peptides (FCPPs) containing a cell penetrating peptide (CPP) and a short protease-responsive peptide (LGLAG) that can be selectively cleaved by a cancer-related enzyme matrix metalloproteinase-2 (MMP-2), and a therapeutic unit (doxorubicin, DOX). Without MMP-2, this prodrug cannot go inside the cells easily. In the presence of MMP-2, DFP can be cleaved into two parts. One is cell penetrating peptides (CPPs) linked DOX, which can easily interact with cell membrane and then go inside the cell with the help of CPPs. Another is the PyTPE modified peptide which will self-aggregate because of the hydrophobic interaction and turn on the yellow fluorescence of PyTPE. The appearance of the yellow fluorescence indicates the release of the therapeutic unit to the cells. The selective delivery of the drug to the MMP-2 positive cells was also confirmed by using the intrinsic red fluorescence of DOX. Our result suggests a new and promising method for controlled drug delivery and real-time tracking of drug release in MMP-2 overexpression cells.
authors: Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, P. R. China.|National Engineering Research Center for Nanomedicine, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, P. R. China.
authors: Yong
authors: Y
authors: Cheng
authors: Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, P. R. China.
authors: Fujian
authors: F
authors: Huang
authors: Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, P. R. China.
authors: Xuehong
authors: X
authors: Min
authors: Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, P. R. China.
authors: Pengcheng
authors: P
authors: Gao
authors: Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, P. R. China.
authors: Tianchi
authors: T
authors: Zhang
authors: Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, P. R. China.
authors: Xinchun
authors: X
authors: Li
authors: National Engineering Research Center for Nanomedicine, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, P. R. China.
authors: Bifeng
authors: B
authors: Liu
authors: School of Chemistry, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors: Yuning
authors: Y
authors: Hong
authors: Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, P. R. China.|Shenzhen Institute of Huazhong University of Science & Technology , Shenzhen 518000, P. R. China.
authors: Xiaoding
authors: X
authors: Lou
authors: Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, P. R. China.|National Engineering Research Center for Nanomedicine, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, P. R. China.|Shenzhen Institute of Huazhong University of Science & Technology , Shenzhen 518000, P. R. China.
authors: Fan
authors: F
authors: Xia
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004354:Drug Screening Assays, Antitumor; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D018613:Microscopy, Confocal; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D057846:Cell-Penetrating Peptides; D005456:Fluorescent Dyes; D011355:Prodrugs; D013267:Stilbenes; C000617116:tetraphenylethylene; D004317:Doxorubicin; D020778:Matrix Metalloproteinase 2