{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:48:58Z","timestamp":1790138938823,"version":"4.0.1"},"reference-count":129,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Cancer is still one of the leading causes of death worldwide. This great mortality is due to its late diagnosis when the disease is already at advanced stages. Although the efforts made to develop more effective treatments, around 90% of cancer deaths are due to metastasis that confers a systemic character to the disease. Likewise, matrix metalloproteinases (MMPs) are endopeptidases that participate in all the events of the metastatic process. MMPs\u2019 augmented concentrations and an increased enzymatic activity have been considered bad prognosis markers of the disease. Therefore, synthetic inhibitors have been created to block MMPs\u2019 enzymatic activity. However, they have been ineffective in addition to causing considerable side effects. On the other hand, nanotechnology offers the opportunity to formulate therapeutic agents that can act directly on a target cell, avoiding side effects and improving the diagnosis, follow-up, and treatment of cancer. The goal of the present review is to discuss novel nanotechnological strategies in which MMPs are used with theranostic purposes and as therapeutic targets to control cancer progression.<\/jats:p>","DOI":"10.3389\/fmolb.2022.918789","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T07:37:07Z","timestamp":1654069027000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment"],"prefix":"10.3389","volume":"9","author":[{"given":"Georgina","family":"Gonzalez-Avila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Armando","family":"Garc\u00eda-Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Flores-Soto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e20190218","DOI":"10.1084\/jem.20190218","article-title":"Emerging Paradigms in Metastasis Research","volume":"218","author":"Abdul Pari","year":"2021","journal-title":"J. Exp. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1700808","DOI":"10.1002\/adhm.201700808","article-title":"An Inexpensive, Point-Of-Care Urine Test for Bladder Cancer in Patients Undergoing Hematuria Evaluation","volume":"6","author":"Acharya","year":"2017","journal-title":"Adv. Healthc. Mat."},{"key":"B3","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.semcancer.2017.11.008","article-title":"Matrix Metalloproteinases: A Challenging Paradigm of Cancer Management","volume":"56","author":"Alaseem","year":"2019","journal-title":"Seminars Cancer Biol."},{"key":"B4","first-page":"215","article-title":"Matrix Metalloproteinases Involvement in Pathologic Conditions","volume":"51","author":"Am\u0103linei","year":"2010","journal-title":"Rom. J. Morphol. Embryol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/btm2.10003","article-title":"Nanoparticles in the Clinic","volume":"1","author":"Anselmo","year":"2016","journal-title":"Bioeng. Transl. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"4734","DOI":"10.3390\/ijms21134734","article-title":"Effects of DSPP and MMP20 Silencing on Adhesion, Metastasis, Angiogenesis, and Epithelial-Mesenchymal Transition Proteins in Oral Squamous Cell Carcinoma Cells","volume":"21","author":"Aseervatham","year":"2020","journal-title":"Ijms"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1002\/ijc.29519","article-title":"HIF-1 at the Crossroads of Hypoxia, Inflammation, and Cancer","volume":"138","author":"Balamurugan","year":"2016","journal-title":"Int. J. Cancer"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1083\/jcb.201804161","article-title":"Glutathione Metabolism in Cancer Progression and Treatment Resistance","volume":"217","author":"Bansal","year":"2018","journal-title":"J. Cell. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1002\/path.4493","article-title":"Stromal Matrix Metalloproteinase 2 Regulates Collagen Expression and Promotes the Outgrowth of Experimental Metastases","volume":"235","author":"Bates","year":"2015","journal-title":"J. Pathol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"112","DOI":"10.3390\/molecules25010112","article-title":"The History of Nanoscience and Nanotechnology: From Chemical-Physical Applications to Nanomedicine","volume":"25","author":"Bayda","year":"2019","journal-title":"Molecules"},{"key":"B11","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1039\/c4nr05269b","article-title":"Dual-radiolabeled Nanoparticle SPECT Probes for Bioimaging","volume":"7","author":"Black","year":"2015","journal-title":"Nanoscale"},{"key":"B12","doi-asserted-by":"publisher","first-page":"198","DOI":"10.4161\/cbt.10.2.12193","article-title":"Stromelysin-1 (MMP-3) Is a Target and a Regulator of Wnt1-Induced Epithelial-Mesenchymal Transition (EMT)","volume":"10","author":"Blavier","year":"2010","journal-title":"Cancer Biol. Ther."},{"key":"B13","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/bs.acr.2015.04.013","article-title":"Phagocytes as Corrupted Policemen in Cancer-Related Inflammation","volume":"128","author":"Bonavita","year":"2015","journal-title":"Adv. Cancer Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"28132","DOI":"10.18632\/oncotarget.4654","article-title":"RUNX2 and TAZ-dependent Signaling Pathways Regulate Soluble E-Cadherin Levels and Tumorsphere Formation in Breast Cancer Cells","volume":"6","author":"Brusgard","year":"2015","journal-title":"Oncotarget"},{"key":"B15","doi-asserted-by":"publisher","first-page":"6232","DOI":"10.1074\/jbc.M705759200","article-title":"Membrane Type 1 Matrix Metalloproteinase Induces Epithelial-To-Mesenchymal Transition in Prostate Cancer","volume":"283","author":"Cao","year":"2008","journal-title":"J. Biol. Chem."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1021\/acssensors.8b00320","article-title":"Rational Engineering a Multichannel Upconversion Sensor for Multiplex Detection of Matrix Metalloproteinase Activities","volume":"3","author":"Cao","year":"2018","journal-title":"ACS Sens."},{"key":"B17","doi-asserted-by":"publisher","first-page":"5598","DOI":"10.18632\/oncotarget.6798","article-title":"Targeting the Warburg Effect in Cancer Cells through ENO1 Knockdown Rescues Oxidative Phosphorylation and Induces Growth Arrest","volume":"7","author":"Capello","year":"2016","journal-title":"Oncotarget"},{"key":"B18","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1101\/gad.277681.116","article-title":"Distinctive Properties of Metastasis-Initiating Cells","volume":"30","author":"Celi\u00e0-Terrassa","year":"2016","journal-title":"Genes. Dev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.2217\/nnm-2018-0524","article-title":"Development of Upconversion Nanoparticle-Conjugated Indium Phosphide Quantum Dot for Matrix Metalloproteinase-2 Cancer Transformation Sensing","volume":"14","author":"Chan","year":"2019","journal-title":"Nanomedicine"},{"key":"B20","doi-asserted-by":"publisher","first-page":"672195","DOI":"10.3389\/fonc.2021.672195","article-title":"Early Dissemination of Circulating Tumor Cells: Biological and Clinical Insights","volume":"11","author":"Chemi","year":"2021","journal-title":"Front. Oncol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"538","DOI":"10.7150\/thno.16684","article-title":"Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment","volume":"7","author":"Chen","year":"2017","journal-title":"Theranostics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.taap.2016.09.007","article-title":"Gallic Acid-Capped Gold Nanoparticles Inhibit EGF-Induced MMP-9 Expression through Suppression of P300 Stabilization and NF\u03baB\/c-Jun Activation in Breast Cancer MDA-MB-231 Cells","volume":"310","author":"Chen","year":"2016","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2878","DOI":"10.7150\/thno.19358","article-title":"Blood Droplet-Based Cancer Diagnosis via Proteolytic Activity Measurement in Cancer Progression","volume":"7","author":"Choi","year":"2017","journal-title":"Theranostics"},{"key":"B24","doi-asserted-by":"publisher","first-page":"88","DOI":"10.4048\/jbc.2011.14.2.88","article-title":"Overexpression of MMP-9 and HIF-1\u03b1 in Breast Cancer Cells under Hypoxic Conditions","volume":"14","author":"Choi","year":"2011","journal-title":"J. Breast Cancer"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.pmbts.2017.02.005","article-title":"Biochemical and Biological Attributes of Matrix Metalloproteinases","volume":"147","author":"Cui","year":"2017","journal-title":"Prog. Mol. Biol.Transl. Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"9935","DOI":"10.1039\/c8nr00640g","article-title":"A Size Switchable Nanoplatform for Targeting the Tumor Microenvironment and Deep Tumor Penetration","volume":"10","author":"Cun","year":"2018","journal-title":"Nanoscale"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1016\/j.tibtech.2017.09.001","article-title":"Challenges of the Nano-Bio Interface in Lateral Flow and Dipstick Immunoassays","volume":"35","author":"de Puig","year":"2017","journal-title":"Trends Biotechnol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"5574","DOI":"10.1002\/cam4.2474","article-title":"Are 90% of Deaths from Cancer Caused by Metastases?","volume":"8","author":"Dillek\u00e5s","year":"2019","journal-title":"Cancer Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1002\/ijc.33588","article-title":"Cancer Statistics for the Year 2020: An Overview","volume":"149","author":"Ferlay","year":"2021","journal-title":"Int. J. Cancer"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2867","DOI":"10.21873\/anticanres.11639","article-title":"The Immunological Roles of Periostin\/tumor-Associated Macrophage axis in Development of Dermatofibrosarcoma Protuberans","volume":"37","author":"Fujimura","year":"2017","journal-title":"Ar"},{"key":"B31","doi-asserted-by":"publisher","first-page":"793","DOI":"10.3892\/ijo.30.4.793","article-title":"Silencing Hypoxia-Inducible Factor-1\u03b1 Inhibits Cell Migration and Invasion under Hypoxic Environment in Malignant Gliomas","volume":"30","author":"Fujiwara","year":"2007","journal-title":"Int. J. Oncol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1038\/ncb1658","article-title":"Fibroblast-led Collective Invasion of Carcinoma Cells with Differing Roles for RhoGTPases in Leading and Following Cells","volume":"9","author":"Gaggioli","year":"2007","journal-title":"Nat. Cell. Biol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1007\/s00018-013-1431-0","article-title":"Domain Structure and Function of Matrix Metalloprotease 23 (MMP23): Role in Potassium Channel Trafficking","volume":"71","author":"Galea","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2755","DOI":"10.1021\/mp500113p","article-title":"Angiopep-2 and Activatable Cell-Penetrating Peptide Dual-Functionalized Nanoparticles for Systemic Glioma-Targeting Delivery","volume":"11","author":"Gao","year":"2014","journal-title":"Mol. Pharm."},{"key":"B35","doi-asserted-by":"publisher","first-page":"366","DOI":"10.3389\/fonc.2014.00366","article-title":"Emerging Understanding of Multiscale Tumor Heterogeneity","volume":"4","author":"Gerdes","year":"2014","journal-title":"Front. Oncol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/978-3-030-40146-7_5","article-title":"Matrix Metalloproteinases' Role in Tumor Microenvironment","volume":"1245","author":"Gonzalez-Avila","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.critrevonc.2019.02.010","article-title":"Matrix Metalloproteinases Participation in the Metastatic Process and Their Diagnostic and Therapeutic Applications in Cancer","volume":"137","author":"Gonzalez-Avila","year":"2019","journal-title":"Crit. Rev. Oncology\/Hematology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1039\/c2an36128k","article-title":"Toward Development of a Surface-Enhanced Raman Scattering (SERS)-Based Cancer Diagnostic Immunoassay Panel","volume":"138","author":"Granger","year":"2013","journal-title":"Analyst"},{"key":"B39","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: the Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell."},{"key":"B40","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.critrevonc.2015.09.008","article-title":"Paracrine Tumor Signaling Induces Transdifferentiation of Surrounding Fibroblasts","volume":"97","author":"Heneberg","year":"20162016","journal-title":"Crit. Rev. Oncology\/Hematology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e69354","DOI":"10.1371\/journal.pone.0069354","article-title":"Surface \u03b1-Enolase Promotes Extracellular Matrix Degradation and Tumor Metastasis and Represents a New Therapeutic Target","volume":"8","author":"Hsiao","year":"2013","journal-title":"PLoS One"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1007\/s13402-021-00620-1","article-title":"Blocking MMP-12-Modulated Epithelial-Mesenchymal Transition by Repurposing Penfluridol Restrains Lung Adenocarcinoma Metastasis via uPA\/uPAR\/TGF-\u03b2\/Akt Pathway","volume":"44","author":"Hung","year":"2021","journal-title":"Cell. Oncol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"3856","DOI":"10.1242\/jcs.03157","article-title":"Epilysin (MMP-28) Induces TGF-\u03b2 Mediated Epithelial to Mesenchymal Transition in Lung Carcinoma Cells","volume":"119","author":"Illman","year":"2006","journal-title":"J. Cell. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.matbio.2015.03.004","article-title":"Membrane-type Matrix Metalloproteinases: Their Functions and Regulations","author":"Itoh","year":"2015","journal-title":"Matrix Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/1479-7364-4-3-194","article-title":"Update of Human and Mouse Matrix Metalloproteinase Families","volume":"4","author":"Jackson","year":"2010","journal-title":"Hum. Genomics"},{"key":"B46","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s10555-019-09796-3","article-title":"Acidosis and Proteolysis in the Tumor Microenvironment","volume":"38","author":"Ji","year":"2019","journal-title":"Cancer Metastasis Rev."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1700867","DOI":"10.1002\/advs.201700867","article-title":"Drug-Bearing Supramolecular MMP Inhibitor Nanofibers for Inhibition of Metastasis and Growth of Liver Cancer","volume":"5","author":"Ji","year":"2018","journal-title":"Adv. Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"399","DOI":"10.18926\/AMO\/48964","article-title":"HIF-1\u03b1 Contributes to Hypoxia-Induced Invasion and Metastasis of Esophageal Carcinoma via Inhibiting E-Cadherin and Promoting MMP-2 Expression","volume":"66","author":"Jing","year":"2012","journal-title":"Acta Med. Okayama"},{"key":"B49","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s10585-012-9536-7","article-title":"Potentiation of Tumor Cell Invasion by Co-culture with Monocytes Accompanying Enhanced Production of Matrix Metalloproteinase and Fibronectin","volume":"30","author":"Kamoshida","year":"2013","journal-title":"Clin. Exp. Metastasis"},{"key":"B50","doi-asserted-by":"publisher","first-page":"15431","DOI":"10.1073\/pnas.1204600109","article-title":"Molecular Mechanism of Pancreatic Tumor Metastasis Inhibition by Gd@C 82 (OH) 22 and its Implication for De Novo Design of Nanomedicine","volume":"109","author":"Kang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1007\/s00259-019-04607-x","article-title":"Targeting MMP-14 for Dual PET and Fluorescence Imaging of Glioma in Preclinical Models","volume":"47","author":"Kasten","year":"2020","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"B52","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.cell.2010.03.015","article-title":"Matrix Metalloproteinases: Regulators of the Tumor Microenvironment","volume":"141","author":"Kessenbrock","year":"2010","journal-title":"Cell."},{"key":"B53","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/B978-0-08-100716-7.00014-3","article-title":"Nanoparticles for Biomedical Applications: An Overview","volume-title":"Nanobiomaterials","author":"Khan","year":"2018"},{"key":"B54","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s12272-020-01214-5","article-title":"Photodynamic Therapy with Smart Nanomedicine","volume":"43","author":"Kim","year":"2020","journal-title":"Arch. Pharm. Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"11476","DOI":"10.1021\/acs.chemrev.7b00194","article-title":"Form Follows Function: Nanoparticle Shape and its Implications for Nanomedicine","volume":"117","author":"Kinnear","year":"2017","journal-title":"Chem. Rev."},{"key":"B56","first-page":"1138","article-title":"Regulation of Colon Carcinoma Cell Invasion by Hypoxia-Inducible Factor 1","volume":"63","author":"Krishnamachary","year":"2003","journal-title":"Cancer Res."},{"key":"B57","doi-asserted-by":"publisher","first-page":"203","DOI":"10.3390\/cells8030203","article-title":"Cathepsin B Is Upregulated and Mediates ECM Degradation in Colon Adenocarcinoma HT29 Cells Overexpressing Snail","volume":"8","author":"Kryczka","year":"2019","journal-title":"Cells"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1016\/j.biopha.2018.07.049","article-title":"Photodynamic Therapy - Mechanisms, Photosensitizers and Combinations","volume":"106","author":"Kwiatkowski","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B59","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.critrevonc.2003.09.008","article-title":"TIMPs as Multifacial Proteins","volume":"49","author":"Lambert","year":"2004","journal-title":"Crit. Rev. Oncology\/Hematology"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1093\/carcin\/bgp248","article-title":"MMP13 as a Stromal Mediator in Controlling Persistent Angiogenesis in Skin Carcinoma","volume":"31","author":"Lederle","year":"2010","journal-title":"Carcinogenesis"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-981-33-6158-4_1","article-title":"Introduction of Nanobiotechnology","volume":"1309","author":"Lee","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1089\/scd.2013.0632","article-title":"Netrin-1 Induces MMP-12-dependent E-Cadherin Degradation via the Distinct Activation of PKC\u03b1 and FAK\/Fyn in Promoting Mesenchymal Stem Cell Motility","volume":"23","author":"Lee","year":"2014","journal-title":"Stem Cells Dev."},{"key":"B63","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1021\/bc500020g","article-title":"Tumor-homing Glycol Chitosan-Based Optical\/PET Dual Imaging Nanoprobe for Cancer Diagnosis","volume":"25","author":"Lee","year":"2014","journal-title":"Bioconjugate Chem."},{"key":"B64","doi-asserted-by":"publisher","first-page":"233","DOI":"10.7150\/ntno.25565","article-title":"Multifunctional Magnetic Mesoporous Silica Nanoagents for In Vivo Enzyme-Responsive Drug Delivery and MR Imaging","volume":"2","author":"Li","year":"2018","journal-title":"Nanotheranostics"},{"key":"B65","doi-asserted-by":"publisher","first-page":"6883","DOI":"10.1007\/s13277-015-3381-7","article-title":"Decreased MT1-MMP in Gastric Cancer Suppressed Cell Migration and Invasion via Regulating MMPs and EMT","volume":"36","author":"Li","year":"2015","journal-title":"Tumor Biol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"117","DOI":"10.5301\/jbm.5000026","article-title":"Potential Clinical Applications of Matrix Metalloproteinase Inhibitors and Their Future Prospects","volume":"28","author":"Li","year":"2013","journal-title":"Int. J. Biol. Markers"},{"key":"B67","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1111\/j.1349-7006.2011.01861.x","article-title":"Matrix Metalloproteinase-9 Cooperates with Transcription Factor Snail to Induce Epithelial-Mesenchymal Transition","volume":"102","author":"Lin","year":"2011","journal-title":"Cancer Sci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1016\/j.febslet.2008.06.033","article-title":"Hypoxia-inducible Factor-1\u03b1 Regulates Matrix Metalloproteinase-1 Activity in Human Bone Marrow-Derived Mesenchymal Stem Cells","volume":"582","author":"Lin","year":"2008","journal-title":"FEBS Lett."},{"key":"B69","doi-asserted-by":"publisher","first-page":"4314","DOI":"10.1039\/c8tb00489g","article-title":"Transferrin-functionalized Chitosan-Graft-Poly(l-Lysine) Dendrons as a High-Efficiency Gene Delivery Carrier for Nasopharyngeal Carcinoma Therapy","volume":"6","author":"Liu","year":"2018","journal-title":"J. Mat. Chem. B"},{"key":"B70","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1080\/10717544.2019.1642421","article-title":"Transferrin-targeting Redox Hyperbranched Poly(amido Amine)-Functionalized Graphene Oxide for Sensitized Chemotherapy Combined with Gene Therapy to Nasopharyngeal Carcinoma","volume":"26","author":"Liu","year":"","journal-title":"Drug Deliv."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1080\/10717544.2019.1698674","article-title":"A Cationic Polymeric Prodrug with Chemotherapeutic Self-Sensibilization Co-delivering MMP-9 shRNA Plasmid for a Combined Therapy to Nasopharyngeal Carcinoma","volume":"26","author":"Liu","year":"","journal-title":"Drug Deliv."},{"key":"B72","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1039\/c8cs00618k","article-title":"Photothermal Therapy and Photoacoustic Imaging via Nanotheranostics in Fighting Cancer","volume":"48","author":"Liu","year":"2019","journal-title":"Chem. Soc. Rev."},{"key":"B73","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1183\/09031936.00146510","article-title":"Biological Role of Matrix Metalloproteinases: a Critical Balance","volume":"38","author":"Loffek","year":"2011","journal-title":"Eur. Respir. J."},{"key":"B74","doi-asserted-by":"publisher","first-page":"5928","DOI":"10.1158\/1078-0432.CCR-10-1360","article-title":"Hypoxia and Hypoxia-Inducible Factors: Master Regulators of Metastasis","volume":"16","author":"Lu","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"B75","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41392-019-0054-9","article-title":"Potent Delivery of an MMP Inhibitor to the Tumor Microenvironment with Thermosensitive Liposomes for the Suppression of Metastasis and Angiogenesis","volume":"4","author":"Lyu","year":"2019","journal-title":"Sig Transduct. Target Ther."},{"key":"B76","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jconrel.2017.11.003","article-title":"Doxorubicin Encapsulated Clicked Gold Nanoparticle Clusters Exhibiting Tumor-specific Disassembly for Enhanced Tumor Localization and Computerized Tomographic Imaging","volume":"269","author":"Mao","year":"2018","journal-title":"J. Control. Release"},{"key":"B77","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.phrs.2016.09.033","article-title":"The Thiirane-Based Selective MT1-MMP\/MMP2 Inhibitor ND-322 Reduces Melanoma Tumor Growth and Delays Metastatic Dissemination","volume":"113","author":"Marusak","year":"2016","journal-title":"Pharmacol. Res."},{"key":"B78","doi-asserted-by":"publisher","first-page":"3127","DOI":"10.2217\/nnm-2019-0298","article-title":"Hampering Brain Tumor Proliferation and Migration Using Peptide nanofiber:siPLK1\/MMP2 Complexes","volume":"14","author":"Mazza","year":"2019","journal-title":"Nanomedicine"},{"key":"B79","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1016\/j.bbamcr.2017.04.011","article-title":"Selective Small-Molecule Inhibitors as Chemical Tools to Define the Roles of Matrix Metalloproteinases in Disease","volume":"1864","author":"Meisel","year":"2017","journal-title":"Biochimica Biophysica Acta (BBA) - Mol. Cell. Res."},{"key":"B80","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/j.1699-0463.1999.tb01524.x","article-title":"Mechanisms for Pro Matrix Metalloproteinase Activation","volume":"107","author":"Murphy","year":"1999","journal-title":"APMIS"},{"key":"B81","doi-asserted-by":"publisher","first-page":"91","DOI":"10.7150\/thno.34851","article-title":"Matrix Metalloproteinase-Sensitive Multistage Nanogels Promote Drug Transport in 3D Tumor Model","volume":"10","author":"Nagel","year":"2020","journal-title":"Theranostics"},{"key":"B82","doi-asserted-by":"publisher","first-page":"6451","DOI":"10.1074\/jbc.M112.421495","article-title":"Intracellular Trafficking of the KV1.3 Potassium Channel Is Regulated by the Prodomain of a Matrix Metalloprotease","volume":"288","author":"Nguyen","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B83","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.bios.2015.12.031","article-title":"Fabrication of Peptide Stabilized Fluorescent Gold Nanocluster\/graphene Oxide Nanocomplex and its Application in Turn-On Detection of Metalloproteinase-9","volume":"89","author":"Nguyen","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"B84","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1242\/jcs.114.1.111","article-title":"Release of an Invasion Promoter E-Cadherin Fragment by Matrilysin and Stromelysin-1","volume":"114","author":"No\u00eb","year":"2001","journal-title":"J. Cell. Sci."},{"key":"B85","doi-asserted-by":"publisher","first-page":"18506","DOI":"10.1074\/jbc.270.31.18506","article-title":"Steps Involved in Activation of the Pro-matrix Metalloproteinase 9 (Progelatinase B)-tissue Inhibitor of Metalloproteinases-1 Complex by 4-aminophenylmercuric Acetate and Proteinases","volume":"270","author":"Ogata","year":"1995","journal-title":"J. Biol. Chem."},{"key":"B86","doi-asserted-by":"publisher","first-page":"4311","DOI":"10.1073\/pnas.0910283107","article-title":"Activatable Cell Penetrating Peptides Linked to Nanoparticles as Dual Probes for In Vivo Fluorescence and MR Imaging of Proteases","volume":"107","author":"Olson","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B87","doi-asserted-by":"publisher","first-page":"5503","DOI":"10.2174\/1381612826666201116120422","article-title":"Nanotheranostics for Cancer Therapy and Detection: State of the Art","volume":"26","author":"Paliwal","year":"2020","journal-title":"Cpd"},{"key":"B88","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3389\/fbioe.2020.00503","article-title":"Smart Nanotheranostics Responsive to Pathological Stimuli","volume":"8","author":"Parodi","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"2313","DOI":"10.1021\/acsnano.6b06040","article-title":"Diverse Applications of Nanomedicine","volume":"11","author":"Pelaz","year":"2017","journal-title":"ACS Nano"},{"key":"B90","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1186\/s13058-018-1076-x","article-title":"CD68, CD163, and Matrix Metalloproteinase 9 (MMP-9) Co-localization in Breast Tumor Microenvironment Predicts Survival Differently in ER-Positive and -negative Cancers","volume":"20","author":"Pelekanou","year":"2018","journal-title":"Breast Cancer Res."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.103\/jid.2011.910.1038\/jid.2011.9","article-title":"Tumor-associated Macrophages in the Cutaneous SCC Microenvironment Are Heterogeneously Activated","volume":"131","author":"Pettersen","year":"2011","journal-title":"J. Investigative Dermatology"},{"key":"B92","doi-asserted-by":"publisher","first-page":"137","DOI":"10.2116\/analsci.33.137","article-title":"F&ouml;rster Resonance Energy Transfer Mediated Photoluminescence Quenching in Stoichiometrically Assembled CdSe\/ZnS Quantum Dot-Peptide Labeled Black Hole Quencher Conjugates for Matrix Metalloproteinase-2 Sensing","volume":"33","author":"Pillai","year":"2017","journal-title":"Anal. Sci."},{"key":"B93","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/978-1-4939-7595-2_27","article-title":"Strategies to Target Matrix Metalloproteinases as Therapeutic Approach in Cancer","volume":"1731","author":"Piperigkou","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.matbio.2007.07.001","article-title":"Control of Matrix Metalloproteinase Catalytic Activity","volume":"26","author":"Ra","year":"2007","journal-title":"Matrix Biol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/nature03688","article-title":"Rac1b and Reactive Oxygen Species Mediate MMP-3-Induced EMT and Genomic Instability","volume":"436","author":"Radisky","year":"2005","journal-title":"Nature"},{"key":"B96","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1126\/science.aaf4405","article-title":"Hypoxic Control of Metastasis","volume":"352","author":"Rankin","year":"2016","journal-title":"Science"},{"key":"B97","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1111\/exd.12435","article-title":"Matricryptins and Matrikines: Biologically Active Fragments of the Extracellular Matrix","volume":"23","author":"Ricard-Blum","year":"2014","journal-title":"Exp. Dermatol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1021\/acsnano.0c09382","article-title":"Hybrid Nanosystems for Biomedical Applications","volume":"15","author":"Seaberg","year":"2021","journal-title":"ACS Nano"},{"key":"B99","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/s41419-018-0425-0","article-title":"Hypoxia-induced Matrix Metalloproteinase-13 Expression in Exosomes from Nasopharyngeal Carcinoma Enhances Metastases","volume":"9","author":"Shan","year":"2018","journal-title":"Cell. Death Dis."},{"key":"B100","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/nrc.2016.108","article-title":"Cancer Nanomedicine: Progress, Challenges and Opportunities","volume":"17","author":"Shi","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"B101","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1016\/j.yexcr.2007.01.013","article-title":"Hypoxia-inducible Factor 1\u03b1 Regulates Lung Adenocarcinoma Cell Invasion","volume":"313","author":"Shyu","year":"2007","journal-title":"Exp. Cell. Res."},{"key":"B102","doi-asserted-by":"publisher","first-page":"4111","DOI":"10.1007\/s00018-015-1995-y","article-title":"Macrophage Polarization in Pathology","volume":"72","author":"Sica","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"B103","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s10555-007-9062-2","article-title":"Hypoxia-driven Selection of the Metastatic Phenotype","volume":"26","author":"Sullivan","year":"2007","journal-title":"Cancer Metastasis Rev."},{"key":"B104","doi-asserted-by":"publisher","first-page":"2030","DOI":"10.1158\/0008-5472.CAN-06-2808","article-title":"Engagement of Collagen-Binding Integrins Promotes Matrix Metalloproteinase-9-dependent E-Cadherin Ectodomain Shedding in Ovarian Carcinoma Cells","volume":"67","author":"Symowicz","year":"2007","journal-title":"Cancer Res."},{"key":"B105","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.bbamcr.2009.04.003","article-title":"Matrix Metalloproteinases: Fold and Function of Their Catalytic Domains","volume":"1803","author":"Tallant","year":"2010","journal-title":"Biochimica Biophysica Acta (BBA) - Mol. Cell. Res."},{"key":"B106","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.actbio.2018.01.014","article-title":"Self-sensibilized Polymeric Prodrug Co-delivering MMP-9 shRNA Plasmid for Combined Treatment of Tumors","volume":"69","author":"Tang","year":"2018","journal-title":"Acta Biomater."},{"key":"B107","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1007\/s10555-014-9530-4","article-title":"New Approaches to Selectively Target Cancer-Associated Matrix Metalloproteinase Activity","volume":"33","author":"Tauro","year":"2014","journal-title":"Cancer Metastasis Rev."},{"key":"B108","doi-asserted-by":"publisher","first-page":"112027","DOI":"10.1016\/j.msec.2021.112027","article-title":"Efficient, Enzyme Responsive and Tumor Receptor Targeting Gelatin Nanoparticles Decorated with Concanavalin-A for Site-specific and Controlled Drug Delivery for Cancer Therapy","volume":"123","author":"Vaghasiya","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"B109","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1021\/ac202627b","article-title":"Upconversion Fluorescence Resonance Energy Transfer Based Biosensor for Ultrasensitive Detection of Matrix Metalloproteinase-2 in Blood","volume":"84","author":"Wang","year":"2012","journal-title":"Anal. Chem."},{"key":"B110","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1158\/jcr.1925.148","article-title":"The Metabolism of Carcinoma Cells","volume":"9","author":"Warburg","year":"1925","journal-title":"J. Cancer Res."},{"key":"B111","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1080\/10717544.2021.1931560","article-title":"A Size-Shrinkable Matrix Metallopeptidase-2-Sensitive Delivery Nanosystem Improves the Penetration of Human Programmed Death-Ligand 1 siRNA into Lung-Tumor Spheroids","volume":"28","author":"Wen","year":"2021","journal-title":"Drug Deliv."},{"key":"B112","doi-asserted-by":"publisher","first-page":"e773","DOI":"10.14800\/ccm.773","article-title":"Tumor Talk: Understanding the Conversation between the Tumor and its Microenvironment","volume":"2","author":"Whipple","year":"2015","journal-title":"Can. Cell. Microenviron."},{"key":"B113","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1158\/1535-7163.MCT-17-0646","article-title":"Matrix Metalloproteinase Inhibitors in Cancer Therapy: Turning Past Failures into Future Successes","volume":"17","author":"Winer","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"B114","doi-asserted-by":"publisher","first-page":"14596","DOI":"10.1021\/acsami.6b15853","article-title":"Design and Proof of Programmed 5-aminolevulinic Acid Prodrug Nanocarriers for Targeted Photodynamic Cancer Therapy","volume":"9","author":"Wu","year":"2017","journal-title":"ACS Appl. Mat. Interfaces"},{"key":"B115","doi-asserted-by":"publisher","first-page":"771","DOI":"10.3390\/jpm11080771","article-title":"The Enhanced Permeability and Retention (EPR) Effect: The Significance of the Concept and Methods to Enhance its Application","volume":"11","author":"Wu","year":"2021","journal-title":"Jpm"},{"key":"B116","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1021\/acsabm.9b01049","article-title":"Activatable Cell-Penetrating Peptide Conjugated Polymeric Nanoparticles with Gd-Chelation and Aggregation-Induced Emission for Bimodal MR and Fluorescence Imaging of Tumors","volume":"3","author":"Xia","year":"2020","journal-title":"ACS Appl. Bio Mat."},{"key":"B117","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.actbio.2019.03.008","article-title":"Matrix Metallopeptidase 2 Targeted Delivery of Gold Nanostars Decorated with IR-780 Iodide for Dual-Modal Imaging and Enhanced Photothermal\/photodynamic Therapy","volume":"89","author":"Xia","year":"2019","journal-title":"Acta Biomater."},{"key":"B118","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1080\/02652048.2017.1343873","article-title":"Matrix Metalloproteases-Responsive Nanomaterials for Tumor Targeting Diagnosis and Treatment","volume":"34","author":"Xiong","year":"2017","journal-title":"J. Microencapsul."},{"key":"B119","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.3390\/cancers7040876","article-title":"Direct Interaction between Carcinoma Cells and Cancer Associated Fibroblasts for the Regulation of Cancer Invasion","volume":"7","author":"Yamaguchi","year":"2015","journal-title":"Cancers"},{"key":"B120","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/1471-2407-13-171","article-title":"Membrane Type 1 Matrix Metalloproteinase Induces an Epithelial to Mesenchymal Transition and Cancer Stem Cell-like Properties in SCC9 Cells","volume":"13","author":"Yang","year":"2013","journal-title":"BMC Cancer"},{"key":"B121","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1517\/17425255.2016.1131820","article-title":"Pharmacodynamic Considerations in the Use of Matrix Metalloproteinase Inhibitors in Cancer Treatment","volume":"12","author":"Yang","year":"2016","journal-title":"Expert Opin. Drug Metabolism Toxicol."},{"key":"B122","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.tips.2018.06.003","article-title":"MMP-responsive 'Smart' Drug Delivery and Tumor Targeting","volume":"39","author":"Yao","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"B123","doi-asserted-by":"publisher","first-page":"4465","DOI":"10.2147\/DDDT.S270303","article-title":"Enhancement of Pancreatic Cancer Therapy Efficacy by Type-1 Matrix Metalloproteinase-Functionalized Nanoparticles for the Selective Delivery of Gemcitabine and Erlotinib","author":"Yin","year":"2020","journal-title":"Dddt"},{"key":"B124","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s11671-021-03489-z","article-title":"Nanoparticles: A New Approach to Upgrade Cancer Diagnosis and Treatment","volume":"16","author":"Yu","year":"2021","journal-title":"Nanoscale Res. Lett."},{"key":"B125","doi-asserted-by":"publisher","first-page":"7202","DOI":"10.12659\/MSM.916886","article-title":"Hypoxia-Inducible Factor-1\u03b1 (HIF-1\u03b1) Promotes Hypoxia-Induced Invasion and Metastasis in Ovarian Cancer by Targeting Matrix Metallopeptidase 13 (MMP13)","volume":"25","author":"Zhang","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"B126","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/978-3-030-58174-9_6","article-title":"Clearable Nanoparticles for Cancer Photothermal Therapy","volume":"1295","author":"Zhao","year":"2021","journal-title":"Exp. Med. Biol."},{"key":"B127","doi-asserted-by":"publisher","first-page":"14998","DOI":"10.1038\/ncomms14998","article-title":"Dual-stimuli Responsive and Reversibly Activatable Theranostic Nanoprobe for Precision Tumor-Targeting and Fluorescence-Guided Photothermal Therapy","volume":"8","author":"Zhao","year":"2017","journal-title":"Nat. Commun."},{"key":"B128","doi-asserted-by":"publisher","first-page":"12609","DOI":"10.1021\/acsami.6b01611","article-title":"Star-shaped Amphiphilic Hyperbranched Polyglycerol Conjugated with Dendritic Poly(l-Lysine) for the Codelivery of Docetaxel and MMP-9 siRNA in Cancer Therapy","volume":"8","author":"Zhou","year":"2016","journal-title":"ACS Appl. Mat. Interfaces"},{"key":"B129","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1002\/mc.20678","article-title":"Transcriptional Upregulation of MT2-MMP in Response to Hypoxia Is Promoted by HIF-1\u03b1 in Cancer Cells","volume":"50","author":"Zhu","year":"2011","journal-title":"Mol. Carcinog."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2022.918789\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T07:37:13Z","timestamp":1654069033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2022.918789\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,1]]},"references-count":129,"alternative-id":["10.3389\/fmolb.2022.918789"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2022.918789","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,1]]},"article-number":"918789"}}