Cited by 262Nanoparticle-Based Drug DeliveryTuberculosis Research and EpidemiologyMesoporous Materials and Catalysis

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Targeted Intracellular Delivery of Antituberculosis Drugs to Mycobacterium tuberculosis-Infected Macrophages via Functionalized Mesoporous Silica Nanoparticles

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Clemens, Daniel L., Lee, Bai-Yu, Xue, Min, Thomas, Courtney R., Meng, Huan, Ferris, Daniel, Nel, Andre E., Zink, Jeffrey I., Horwitz, Marcus A.·2012·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.06049-11PMC PMC3346638

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Abstract

Delivery of antituberculosis drugs by nanoparticles offers potential advantages over free drug, including the potential to target specifically the tissues and cells that are infected by Mycobacterium tuberculosis , thereby simultaneously increasing therapeutic efficacy and decreasing systemic toxicity, and the capacity for prolonged release of drug, thereby allowing less-frequent dosing. We have employed mesoporous silica nanoparticle (MSNP) drug delivery systems either equipped with a polyethyleneimine (PEI) coating to release rifampin or equipped with cyclodextrin-based pH-operated valves that open only at acidic pH to release isoniazid (INH) into M. tuberculosis -infected macrophages. The MSNP are internalized efficiently by human macrophages, traffic to acidified endosomes, and release high concentrations of antituberculosis drugs intracellularly. PEI-coated MSNP show much greater loading of rifampin than uncoated MSNP and much greater efficacy against M. tuberculosis- infected macrophages. MSNP were devoid of cytotoxicity at the particle doses employed for drug delivery. Similarly, we have demonstrated that the isoniazid delivered by MSNP equipped with pH-operated nanovalves kill M. tuberculosis within macrophages significantly more effectively than an equivalent amount of free drug. These data demonstrate that MSNP provide a versatile platform that can be functionalized to optimize the loading and intracellular release of specific drugs for the treatment of tuberculosis.

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Authors: Clemens, D. L., Lee, B.-Y., Xue, M., Thomas, C. R., Meng, H., Ferris, D., Nel, A. E., Zink, J. I., & Horwitz, M. A.
Affiliations: University of California, Los Angeles (US)
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, California, USA
California NanoSystems Institute (US)
ORCID: Clemens, Daniel L.
Lee, Bai-Yu
Xue, Min
Meng, Huan
Ferris, Daniel
Zink, Jeffrey I.
Horwitz, Marcus A.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2012-05
Volume: 56
Issue: 5
Pages: 2535-2545
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.06049-11
PMC: PMC3346638
OpenAlex: W2021068830
Cited by: 260
References: 49
Citations by year: 2026: 12 · 2025: 8 · 2024: 17 · 2023: 24 · 2022: 24 · 2021: 29 · 2020: 24 · 2019: 22 · 2018: 14 · 2017: 16 · 2016: 15 · 2015: 21 · 2014: 21 · 2013: 8 · 2012: 2
FWCI: 6.74
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders: Foundation for the National Institutes of Health
Bill and Melinda Gates Foundation
National Cancer Institute (R01CA133697, CA 133697)
Topics: Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
Physical Sciences › Materials Science › Materials Chemistry › Mesoporous Materials and Catalysis
Keywords: mesoporous silica nanoparticles, Mycobacterium tuberculosis, infected macrophages, rifampicin, isoniazid, polyethyleneimine coating, intracellular drug release, endosomal acidification, tuberculosis treatment
MeSH terms: Antitubercular Agents, Cell Line, Cell Survival, Cyclodextrins, Drug Compounding, Humans, Hydrogen-Ion Concentration, Isoniazid, Macrophages, Mycobacterium tuberculosis, Phagocytosis, Polyethyleneimine, Rifampin, Silicon Dioxide, Colony Count, Microbial, Porosity, Drug Delivery Systems, Microscopy, Electron, Transmission, Microbial Viability, Nanoparticles

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Targeted Intracellular Delivery of Antituberculosis Drugs to Mycobacterium tuberculosis-Infected Macrophages via Functionalized Mesoporous Silica Nanoparticles

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