{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T23:11:03Z","timestamp":1769641863377,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. This paper deals with the synthesis of the polymeric nanoparticle platform, which was produced by Ring-Opening Metathesis Polymerization (ROMP), able to release anti-cancer drugs in dispersion, such as histone deacetylase inhibitors, into mesothelioma tumors. The core-shell nanoparticles (NPs) have stealth properties due to their poly(ethylene oxide) shell and can be viewed as universal nano-carriers on which any alkyne-modified anti-cancer molecule can be grafted by click chemistry. A cleavage reaction of the chemical bond between NPs and drugs through the contact of NPs with a medium presenting an acidic pH, which is typically a cancer tumor environment or an acidic intracellular compartment, induces a controlled release of the bioactive molecule in its native form. In our in vivo syngeneic model of mesothelioma, a highly selective accumulation of the particles in the tumor was obtained. The release of the drugs led to an 80% reduction of tumor weight for the best compound without toxicity. Our work demonstrates that the use of theranostic nanovectors leads to an optimized delivery of epigenetic inhibitors in tumors, which improves their anti-tumor properties in vivo.<\/jats:p>","DOI":"10.3390\/biom9020060","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T02:49:44Z","timestamp":1550026184000},"page":"60","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8171-2031","authenticated-orcid":false,"given":"Philippe","family":"Bertrand","sequence":"first","affiliation":[{"name":"Institut de Chimie des Milieux et Mat\u00e9riaux de Poitiers, UMR CNRS 7285, 4 rue Michel Brunet, TSA 51106, B28, 86073 Poitiers CEDEX 09, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0917-3747","authenticated-orcid":false,"given":"Christophe","family":"Blanquart","sequence":"additional","affiliation":[{"name":"CRCINA, INSERM, Universit\u00e9 d\u2019Angers, Universit\u00e9 de Nantes, 44007 Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9rie","family":"H\u00e9roguez","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie des Polym\u00e8res Organiques, CNRS, UMR 5629, Bordeaux, 16 Avenue Pey-Berland, F-33607 Pessac, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,12]]},"reference":[{"key":"ref_1","first-page":"6","article-title":"L\u2019\u00e9pig\u00e9n\u00e9tique: Enjeux scientifiques, \u00e9thiques et soci\u00e9taux","volume":"407","author":"Monneret","year":"2016","journal-title":"l\u2019Actualit\u00e9 Chimique"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nrd3674","article-title":"Epigenetic protein families: A new frontier for drug discovery","volume":"11","author":"Arrowsmith","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1517\/13543784.16.7.1111","article-title":"Vorinostat: A new oral histone deacetylase inhibitor approved for cutaneous T-cell lymphoma","volume":"16","author":"Duvic","year":"2007","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1586\/era.10.88","article-title":"Romidepsin: A new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors","volume":"10","author":"Grant","year":"2010","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1007\/s40265-014-0275-8","article-title":"Belinostat: First Global Approval","volume":"74","author":"Poole","year":"2014","journal-title":"Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Fenichel, M.P. (2015). FDA Approves New Agent for Multiple Myeloma. J. Natl. Cancer Inst., 107.","DOI":"10.1093\/jnci\/djv165"},{"key":"ref_7","first-page":"117","article-title":"Interpreting clinical assays for histone deacetylase inhibitors","volume":"3","author":"Martinet","year":"2011","journal-title":"Cancer Manag. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.addr.2015.01.002","article-title":"Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity","volume":"91","author":"Maeda","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1254\/jjp.41.163","article-title":"Characterization of vascular permeability-increasing component isolated from solid tumors and the effect of highly polymerized dextran sulfate on its activity","volume":"41","author":"Sato","year":"1986","journal-title":"Jpn. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yang, Y., Sun, H., Liu, Y., Hou, W., Yang, Y., Cai, R., Cui, C., Zhang, P., Pan, X., and Li, X. (2018). Self-assembled aptamer-grafted hyperbranched polymer nanocarrier for targeted and photoresponsive drug delivery. Ang. Chem. Int. Ed.","DOI":"10.1002\/anie.201809753"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3787","DOI":"10.1002\/jps.23265","article-title":"Vorinostat with sustained exposure and high solubility in poly(ethylene glycol)-b-poly(DL-lactic acid) micelle nanocarriers: Characterization and effects on pharmacokinetics in rat serum and urine","volume":"101","author":"Mohamed","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1007\/s11095-014-1300-z","article-title":"Development of vorinostat-loaded solid lipid nanoparticles to enhance pharmacokinetics and efficacy against multidrug-resistant cancer cells","volume":"31","author":"Tran","year":"2014","journal-title":"Pharm. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.biopha.2014.07.015","article-title":"Biocompatibility and biodistribution of suberoylanilide hydroxamic acid loaded poly (DL-lactide-co-glycolide) nanoparticles for targeted drug delivery in cancer","volume":"68","author":"Sankar","year":"2014","journal-title":"Biomed. Pharmacother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.msec.2015.02.037","article-title":"Nanostructured delivery system for Suberoylanilide hydroxamic acid against lung cancer cells","volume":"51","author":"Sankar","year":"2015","journal-title":"Mater. Sci. Eng. C. Mater. Biol. Appl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.biomaterials.2015.02.015","article-title":"Nanoparticle formulations of histone deacetylase inhibitors for effective chemoradiotherapy in solid tumors","volume":"51","author":"Wang","year":"2015","journal-title":"Biomaterials"},{"key":"ref_16","unstructured":"Tran, T., Chu, D., Truong, D., Tak, J., Jeong, J., Hoang, V., Yong, C., and Kim, J. (2015). Development of lipid nanoparticles for a histone deacetylases inhibitor as a promising anticancer therapeutic. Drug Deliv., 1\u20139."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"231","DOI":"10.18433\/J3XP4R","article-title":"Modulation of butyrate anticancer activity by solid lipid nanoparticle delivery: An in vitro investigation on human breast cancer and leukemia cell lines","volume":"17","author":"Foglietta","year":"2014","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.carbpol.2014.08.026","article-title":"Hyaluronic acid-coated solid lipid nanoparticles for targeted delivery of vorinostat to CD44 overexpressing cancer cells","volume":"114","author":"Tran","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.biomaterials.2015.07.033","article-title":"Disulfide cross-linked micelles of novel HDAC inhibitor thailandepsin A for the treatment of breast cancer","volume":"67","author":"Xiao","year":"2015","journal-title":"Biomaterials"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.nano.2013.05.017","article-title":"Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer","volume":"9","author":"Martin","year":"2013","journal-title":"Nanomedicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12951-015-0122-4","article-title":"Antitumor activity of vorinostat-incorporated nanoparticles against human cholangiocarcinoma cells","volume":"13","author":"Kwak","year":"2015","journal-title":"J. Nanobiotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2217\/nnm-2016-0321","article-title":"Polymeric micelles of suberoylanilide hydroxamic acid to enhance the anticancer potential in vitro and in vivo","volume":"12","author":"Trivedi","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6003","DOI":"10.2147\/IJN.S118727","article-title":"A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy","volume":"11","author":"Han","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_24","unstructured":"Delatouche, R., Bertrand, P., Collette, F., H\u00e9roguez, V., Gueugnon, F., Blanquart, C., and Gr\u00e9goire, M. (2013). Nanovecteurs ou particules polym\u00e8res et leur utilisation comme m\u00e9dicament et\/ou agent de diagnostic. (WO2013001244A1), French Patent."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.ejpb.2013.03.006","article-title":"Design of pH responsive clickable prodrugs applied to histone deacetylases inhibitors: A new strategy for anticancer therapy","volume":"85","author":"Delatouche","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1002\/ejoc.201001677","article-title":"Triazolyl Derivatives for Acidic Release of Alcohols","volume":"11","author":"Mondon","year":"2011","journal-title":"Eur. J. Org. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"795","DOI":"10.7150\/thno.13725","article-title":"Histone Deacetylase Inhibitors Delivery using Nanoparticles with Intrinsic Passive Tumor Targeting Properties for Tumor Therapy","volume":"6","author":"Denis","year":"2016","journal-title":"Theranostic"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1021\/bm400516b","article-title":"Nanoparticles produced by ring-opening metathesis polymerization using norbornenyl-poly(ethylene oxide) as a ligand-free generic platform for highly selective in vivo tumor targeting","volume":"14","author":"Gueugnon","year":"2013","journal-title":"Biomacromolecules"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/pola.26357","article-title":"An easy and effective method to produce functionalized particles for cellular uptake","volume":"51","author":"Collette","year":"2013","journal-title":"J. Polym. Sci. Part A Polym. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"919","DOI":"10.2174\/156800911797264761","article-title":"Pharmacological characterization of histone deacetylase inhibitor and tumor cell-growth inhibition properties of new benzofuranone compounds","volume":"11","author":"Blanquart","year":"2011","journal-title":"Curr. Cancer Drug Targets."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ejmech.2015.03.037","article-title":"Histone deacetylase inhibitor-polymer conjugate nanoparticles for acid-responsive drug delivery","volume":"95","author":"Denis","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4534","DOI":"10.1021\/bm501338r","article-title":"Vorinostat-polymer conjugate nanoparticles for Acid-responsive delivery and passive tumor targeting","volume":"15","author":"Denis","year":"2014","journal-title":"Biomacromolecules"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4504","DOI":"10.18632\/oncotarget.2056","article-title":"New histone deacetylase inhibitors improve cisplatin antitumor properties against thoracic cancer cells","volume":"5","author":"Gueugnon","year":"2014","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1183\/09031936.00081310","article-title":"A 5-aza-2\u2032-deoxycytidine\/valproate combination induces cytotoxic T-cell response against mesothelioma","volume":"38","author":"Leclercq","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1021\/jm9002439","article-title":"Synthesis and modeling of new benzofuranone histone deacetylase inhibitors that stimulate tumor suppressor gene expression","volume":"52","author":"Charrier","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.nano.2016.12.010","article-title":"Synergistic anticancer activity of combined histone deacetylase and proteasomal inhibitor-loaded zein nanoparticles in metastatic prostate cancers","volume":"13","author":"Thapa","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1208\/s12249-017-0863-5","article-title":"Co-delivery of Vorinostat and Etoposide Via Disulfide Cross-Linked Biodegradable Polymeric Nanogels: Synthesis, Characterization, Biodegradation, and Anticancer Activity","volume":"19","author":"Kumar","year":"2018","journal-title":"AAPS PharmSciTech"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14925","DOI":"10.18632\/oncotarget.14742","article-title":"Molecularly targeted co-delivery of a histone deacetylase inhibitor and paclitaxel by lipid-protein hybrid nanoparticles for synergistic combinational chemotherapy","volume":"8","author":"Ruttala","year":"2017","journal-title":"Oncotarget"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jconrel.2017.09.007","article-title":"Supramolecular cisplatin-vorinostat nanodrug for overcoming drug resistance in cancer synergistic therapy","volume":"266","author":"Xu","year":"2017","journal-title":"J. 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