Intrinsic Antibacterial Activity of Nanoparticles Made of β-Cyclodextrins Potentiates Their Effect as Drug Nanocarriers against Tuberculosis
Arnaud Machelart
(1)
,
Giuseppina Salzano
(2)
,
Xue Li
(2)
,
Aurore Demars
(3)
,
Anne-Sophie Debrie
(1)
,
Mario Menendez-Miranda
(2)
,
Elisabetta Pancani
(2)
,
Samuel J Jouny
(1)
,
Eik Hoffmann
(1)
,
Nathalie Deboosere
(1)
,
Imène Belhaouane
(1)
,
Carine Rouanet
(1)
,
Sophie Simar
(4)
,
Smaïl Talahari
(4, 5)
,
Valerie Giannini
(6)
,
Baptiste Villemagne
(7)
,
Marion Flipo
(7)
,
Roland Brosch
(6)
,
Fabrice Nesslany
(4, 5)
,
Benoit Déprez
(7)
,
Eric Muraille
(3, 8)
,
Camille Locht
(1)
,
Alain Baulard
(1)
,
Nicolas Willand
(7)
,
Laleh Majlessi
(6, 7)
,
Ruxandra Gref
(2)
,
Priscille Brodin
(1)
1
CIIL -
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
2 ISMO - Institut des Sciences Moléculaires d'Orsay
3 UNamur - Université de Namur [Namur]
4 IMPECS - Impact de l'environnement chimique sur la santé humaine - ULR 4483
5 Institut Pasteur de Lille
6 Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics
7 M2SV - Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177
8 ULB - Université libre de Bruxelles
2 ISMO - Institut des Sciences Moléculaires d'Orsay
3 UNamur - Université de Namur [Namur]
4 IMPECS - Impact de l'environnement chimique sur la santé humaine - ULR 4483
5 Institut Pasteur de Lille
6 Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics
7 M2SV - Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177
8 ULB - Université libre de Bruxelles
Arnaud Machelart
- Function : Author
- PersonId : 798056
- ORCID : 0000-0002-4444-0011
Xue Li
- Function : Author
- PersonId : 760758
- ORCID : 0000-0003-0254-643X
Samuel J Jouny
- Function : Author
- PersonId : 1015640
Eik Hoffmann
- Function : Author
- PersonId : 1022991
Nathalie Deboosere
- Function : Author
- PersonId : 768200
- ORCID : 0000-0002-2873-5485
Baptiste Villemagne
- Function : Author
- PersonId : 741971
- IdHAL : baptiste-villemagne
- ORCID : 0000-0002-8416-5253
- IdRef : 232282528
Roland Brosch
- Function : Author
- PersonId : 756611
- ORCID : 0000-0003-2587-3863
- IdRef : 152690778
Eric Muraille
- Function : Author
- PersonId : 760226
- ORCID : 0000-0003-1250-5228
- IdRef : 203119169
Alain Baulard
- Function : Author
- PersonId : 1054419
Nicolas Willand
- Function : Author
- PersonId : 742763
- IdHAL : nicolas-willand
- ORCID : 0000-0002-0784-0462
- IdRef : 075245302
Ruxandra Gref
Connectez-vous pour contacter l'auteur
- Function : Correspondent author
- PersonId : 1058571
Connectez-vous pour contacter l'auteur
Priscille Brodin
Connectez-vous pour contacter l'auteur
- Function : Correspondent author
- PersonId : 1015840
Connectez-vous pour contacter l'auteur
Abstract
Multi-drug-resistant tuberculosis (TB) is a major public health problem, concerning about half a million cases each year. Patients hardly adhere to the current strict treatment consisting of more than 10 000 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-β-cyclodextrins (pβCD) are efficient vehicles for pulmonary delivery of powerful combinations of anti-TB drugs. Here, we report that in addition to being efficient drug carriers, pβCD nanoparticles are endowed with intrinsic antibacterial properties. Empty pβCD nanoparticles are able to impair Mycobacterium tuberculosis (Mtb) establishment after pulmonary administration in mice. pβCD hamper colonization of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, pβCD provoke macrophage apoptosis, leading to depletion of infected cells, thus creating a lung microenvironment detrimental to Mtb persistence. Taken together, our results suggest that pβCD 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.