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Patients hardly adhere to the current strict treatment consisting of more than 10\u202f000 tablets over a 2-year period. There is a clear need for efficient and better formulated medications. We have previously shown that nanoparticles made of cross-linked poly-\u03b2-cyclodextrins (p\u03b2CD) are efficient vehicles for pulmonary delivery of powerful combinations of anti-TB drugs. Here, we report that in addition to being efficient drug carriers, p\u03b2CD nanoparticles are endowed with intrinsic antibacterial properties. Empty p\u03b2CD nanoparticles are able to impair Mycobacterium tuberculosis (Mtb) establishment after pulmonary administration in mice. p\u03b2CD hamper colonization of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, p\u03b2CD provoke macrophage apoptosis, leading to depletion of infected cells, thus creating a lung microenvironment detrimental to Mtb persistence. Taken together, our results suggest that p\u03b2CD nanoparticles loaded or not with antibiotics have an antibacterial action on their own and could be used as a carrier in drug regimen formulations effective against TB.<\/jats:p>","DOI":"10.1021\/acsnano.8b07902","type":"journal-article","created":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T17:17:24Z","timestamp":1551460644000},"page":"3992-4007","source":"Crossref","is-referenced-by-count":72,"title":["Intrinsic\nAntibacterial Activity of Nanoparticles\nMade of \u03b2-Cyclodextrins Potentiates Their Effect as Drug\nNanocarriers against Tuberculosis"],"prefix":"10.1021","volume":"13","author":[{"given":"Arnaud","family":"Machelart","sequence":"first","affiliation":[{"name":"Universite\u0301 de Lille , , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Salzano","sequence":"additional","affiliation":[{"name":"Universite\u0301 Paris Sud, Universite\u0301 Paris-Saclay , , ,","place":["Orsay, France, F-91405"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Li","sequence":"additional","affiliation":[{"name":"Universite\u0301 Paris Sud, Universite\u0301 Paris-Saclay , , ,","place":["Orsay, France, F-91405"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Demars","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Namur , , , ,","place":["Narilis, Namur, Belgium, B-5000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Sophie","family":"Debrie","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Menendez-Miranda","sequence":"additional","affiliation":[{"name":"Universite\u0301 Paris Sud, Universite\u0301 Paris-Saclay , , ,","place":["Orsay, France, F-91405"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Pancani","sequence":"additional","affiliation":[{"name":"Universite\u0301 Paris Sud, Universite\u0301 Paris-Saclay , , ,","place":["Orsay, France, F-91405"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Jouny","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eik","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Deboosere","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ime\u0300ne","family":"Belhaouane","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Rouanet","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Simar","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , EA 4483, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smai\u0308l","family":"Talahari","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , EA 4483, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Giannini","sequence":"additional","affiliation":[{"name":"Institut Pasteur , , CNRS UMR 3525, 25 Rue du Dr. Roux , ,","place":["Paris, France, F-75015"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Villemagne","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , U1177 - Drugs and Molecules for living Systems, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Flipo","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , U1177 - Drugs and Molecules for living Systems, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Brosch","sequence":"additional","affiliation":[{"name":"Institut Pasteur , , CNRS UMR 3525, 25 Rue du Dr. Roux , ,","place":["Paris, France, F-75015"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Nesslany","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , EA 4483, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Deprez","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , U1177 - Drugs and Molecules for living Systems, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Muraille","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Namur , , , ,","place":["Narilis, Namur, Belgium, B-5000"]},{"name":"Universite\u0301 Libre de Bruxelles , , ,","place":["Brussels, Belgium, B-1070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Locht","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Lille , , U1019 - 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UMR 8204 - CIIL - Center for Infection and Immunity of Lille, ,","place":["Lille, France, F-59000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2019,3,1]]},"reference":[{"key":"2026090308473815300_cit1","unstructured":"WHO.\n          \n          Global\nTuberculosis Report 2018. 2018."},{"key":"2026090308473815300_cit2","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1016\/S0140-6736(10)60410-2","article-title":"Multidrug-Resistant\nand Extensively Drug-Resistant Tuberculosis: a Threat to Global Control\nof Tuberculosis","volume":"375","author":"Gandhi","year":"2010","journal-title":"Lancet"},{"key":"2026090308473815300_cit3","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.3389\/fmicb.2017.02284","article-title":"The Macrophage:\nA Disputed Fortress\nin the Battle Against Mycobacterium tuberculosis.","volume":"8","author":"Queval","year":"2017","journal-title":"Front. Microbiol."},{"key":"2026090308473815300_cit4","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1038\/nm.3937","article-title":"The Association\nBetween\nSterilizing Activity and Drug Distribution Into Tuberculosis Lesions","volume":"21","author":"Prideaux","year":"2015","journal-title":"Nat. Med."},{"key":"2026090308473815300_cit5","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.jconrel.2015.11.018","article-title":"Inhaled Drug Treatment\nfor Tuberculosis: Past Progress and Future Prospects","volume":"240","author":"Hickey","year":"2016","journal-title":"J. Controlled Release"},{"key":"2026090308473815300_cit6","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.3389\/fmicb.2016.01831","article-title":"Mechanistic\nBasis of\nAntimicrobial Actions of Silver Nanoparticles","volume":"7","author":"Dakal","year":"2016","journal-title":"Front. Microbiol."},{"key":"2026090308473815300_cit7","doi-asserted-by":"publisher","first-page":"31870","DOI":"10.1021\/acsami.8b09069","article-title":"A Facile Strategy\nEnabling Both High\nLoading and High Release Amounts of the Water-insoluble Drug Clofazimine\nUsing Mesoporous Silica Nanoparticles","volume":"10","author":"Chen","year":"2018","journal-title":"ACS Appl.\nMater. Interfaces"},{"key":"2026090308473815300_cit8","doi-asserted-by":"publisher","first-page":"8732","DOI":"10.1021\/acsnano.6b04207","article-title":"Fully Zwitterionic Nanoparticle Antimicrobial\nAgents through Tuning of Core Size and Ligand Structure","volume":"10","author":"Huo","year":"2016","journal-title":"ACS Nano"},{"key":"2026090308473815300_cit9","doi-asserted-by":"publisher","first-page":"8646","DOI":"10.1021\/acsnano.8b04433","article-title":"Enhanced Permeability and Retention-like\nExtravasation of Nanoparticles From the Vasculature Into Tuberculosis\nGranulomas in Zebrafish and Mouse Models","volume":"12","author":"Fenaroli","year":"2018","journal-title":"ACS\nNano"},{"key":"2026090308473815300_cit10","doi-asserted-by":"publisher","first-page":"7014","DOI":"10.1021\/nn5019126","article-title":"Nanoparticles\nas Drug Delivery System Against Tuberculosis in Zebrafish Embryos:\nDirect Visualization and Treatment","volume":"8","author":"Fenaroli","year":"2014","journal-title":"ACS Nano"},{"key":"2026090308473815300_cit11","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1016\/j.addr.2013.07.011","article-title":"Nanotechnology as\na Therapeutic Tool to Combat Microbial\nResistance","volume":"65","author":"Pelgrift","year":"2013","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026090308473815300_cit12","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/j.apsb.2018.03.008","article-title":"Nanoparticles With High Payloads\nof Pipemidic Acid, a Poorly Soluble Crystalline Drug: Drug-Initiated\nPolymerization and Self-Assembly Approach","volume":"8","author":"Pancani","year":"2018","journal-title":"Acta\nPharm. Sin. B"},{"key":"2026090308473815300_cit13","doi-asserted-by":"publisher","first-page":"5390","DOI":"10.1038\/s41598-017-05453-3","article-title":"Combination\nTherapy for Tuberculosis Treatment: Pulmonary Administration of Ethionamide\nand Booster Co-Loaded Nanoparticles","volume":"7","author":"Costa-Gouveia","year":"2017","journal-title":"Sci. Rep."},{"key":"2026090308473815300_cit14","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/nm.1950","article-title":"Synthetic\nEthR Inhibitors Boost Antituberculous\nActivity of Ethionamide","volume":"15","author":"Willand","year":"2009","journal-title":"Nat. Med."},{"key":"2026090308473815300_cit15","doi-asserted-by":"publisher","first-page":"s41577","DOI":"10.1038\/s41577-019-0124-9","article-title":"Immunometabolism\nat the Interface\nBetween Macrophages and Pathogens","author":"Russell","year":"2019","journal-title":"Nat. Rev.\nImmunol."},{"key":"2026090308473815300_cit16","doi-asserted-by":"publisher","first-page":"28326","DOI":"10.1074\/jbc.M003744200","article-title":"Activation of the\nPro-Drug Ethionamide is Regulated in Mycobacteria","volume":"275","author":"Baulard","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2026090308473815300_cit17","doi-asserted-by":"publisher","first-page":"4876","DOI":"10.1021\/jm500422b","article-title":"Ligand Efficiency\nDriven Design of New Inhibitors of Mycobacterium tuberculosis Transcriptional Repressor EthR Using Fragment Growing, Merging,\nand Linking Approaches","volume":"57","author":"Villemagne","year":"2014","journal-title":"J. Med. Chem."},{"key":"2026090308473815300_cit18","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.ijpharm.2017.05.030","article-title":"Cyclodextrin-Based Nanocarriers Containing\na Synergic Drug Combination:\nA Potential Formulation for Pulmonary Administration of Antitubercular\nDrugs","volume":"531","author":"Salzano","year":"2017","journal-title":"Int. J. Pharm."},{"key":"2026090308473815300_cit19","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1021\/bm801206f","article-title":"Cyclodextrin\nand Polysaccharide-Based\nNanogels: Entrapment of Two Hydrophobic Molecules, Benzophenone and\nTamoxifen","volume":"10","author":"Daoud-Mahammed","year":"2009","journal-title":"Biomacromolecules"},{"key":"2026090308473815300_cit20","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1016\/j.addr.2013.07.020","article-title":"Nanotechnology and\nPulmonary Delivery to Overcome Resistance\nin Infectious Diseases","volume":"65","author":"Andrade","year":"2013","journal-title":"Adv. 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Macromol."},{"key":"2026090308473815300_cit26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jconrel.2005.05.028","article-title":"Pulmonary DNA Vaccination:\nConcepts, Possibilities and Perspectives","volume":"107","author":"Bivas-Benita","year":"2005","journal-title":"J.\nControlled Release"},{"key":"2026090308473815300_cit27","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.tube.2010.08.009","article-title":"Inhaled Drug\nTherapy\nfor Treatment of Tuberculosis","volume":"91","author":"Misra","year":"2011","journal-title":"Tuberculosis"},{"key":"2026090308473815300_cit28","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1093\/jac\/dkh411","article-title":"Lectin-Functionalized\nPoly (Lactide-Co-Glycolide)\nNanoparticles as Oral\/Aerosolized Antitubercular Drug Carriers for\nTreatment of Tuberculosis","volume":"54","author":"Sharma","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"2026090308473815300_cit29","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1177\/0192623307310945","article-title":"Cyclodextrins","volume":"36","author":"Stella","year":"2008","journal-title":"Toxicol. Pathol."},{"key":"2026090308473815300_cit30","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1093\/toxsci\/kfy100","article-title":"Genotoxicity Assessment\nof Nanomaterials: Recommendations on Best Practices, Assays, and Methods","volume":"164","author":"Elespuru","year":"2018","journal-title":"Toxicol. Sci."},{"key":"2026090308473815300_cit31","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1111\/age.12581","article-title":"Cytogenetic Tests for Animal Production: State of the Art and Perspectives","volume":"48","author":"Udroiu","year":"2017","journal-title":"Anim. 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