The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Targeted Intracellular Delivery of Antituberculosis Drugs to Mycobacterium tuberculosis-Infected Macrophages via Functionalized Mesoporous Silica Nanoparticles
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Approximately 90% of MSNP was intracellularly colocalized with CD63 after 3 h of incubation.204”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [204]
In the citing paper
“The majority of the macrophages that were incubated with RITC-labeled NP-RIF internalized the fluorescent nanoparticles and exhibited 10-fold higher fluorescence intensity than the untreated control macrophages.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [204]
In the citing paper
“Drug-specific surface functionalization has been employed for RIF, and further functionalization with poly(ethylene imine) (PEI) yields high loading and controlled drug delivery to MTB-infected macrophages compared to uncoated MSNP.204”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [204]
In the citing paper
“On the other hand, in the case of INH, MSNP decorated with pH-operated nanovalves has been designed to open after endocytosis and endosome acidification to deliver the drug directly to MTB-infected macrophages.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [204]
In the citing paper
“Functionalized MSNP can be internalized efficiently, as confirmed by using human macrophages such as THP-1 cells.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [204]
In the citing paper
“at an acidic pH, the plug is lost, resulting in drug release.”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [66]
Citations
Cites
Boussif, O., Lezoualc’h, F., Zanta, M. A., Djavaheri‐Mergny, M., Scherman, D., DEMENEIX, B. A., & Behr, J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.16.7297 · Cited by 6,256
The effect of particle design on cellular internalization pathways
Gratton, S. E. A., Ropp, P. A., Pohlhaus, P. D., Luft, J. C., Madden, V. J., Napier, M. E., & DeSimone, J. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801763105 · Cited by 2,918
Multifunctional Inorganic Nanoparticles for Imaging, Targeting, and Drug Delivery
Liong, M., Lu, J., Kovochich, M., Xia, T., Ruehm, S. G., Nel, A. E., Tamanoi, F., & Zink, J. I. (2008) · ACS Nano · doi:10.1021/nn800072t · Cited by 1,968
Self-citationLu, J., Liong, M., Li, Z., Zink, J. I., & Tamanoi, F. (2010) · Small · doi:10.1002/smll.201000538 · Cited by 1,095
Self-citationMesoporous Silica Nanoparticles for Intracellular Controlled Drug Delivery
Vivero-Escoto, J. L., Slowing, I. I., Trewyn, B. G., & Lin, V. S. ‐. (2010) · Small · doi:10.1002/smll.200901789 · Cited by 1,024
Mesoporous Silica Nanoparticles as a Delivery System for Hydrophobic Anticancer Drugs
Lu, J., Liong, M., Zink, J. I., & Tamanoi, F. (2007) · Small · doi:10.1002/smll.200700005 · Cited by 1,012
Self-citationThe effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function
Huang, X., Teng, X., Chen, D., Tang, F., & He, J. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.09.060 · Cited by 1,002
Xia, T., Kovochich, M., Liong, M., Meng, H., Kabehie, S., George, S., Zink, J. I., & Nel, A. E. (2009) · ACS Nano · doi:10.1021/nn900918w · Cited by 933
Self-citationMeng, H., Liong, M., Xia, T., Li, Z., Ji, Z., Zink, J. I., & Nel, A. E. (2010) · ACS Nano · doi:10.1021/nn100690m · Cited by 915
Self-citationSilica Particles: A Novel Drug‐Delivery System
Barbe, C., Bartlett, J. R., Kong, L., Finnie, K. S., Lin, H., Larkin, M., Calleja, S., Bush, A. J., & Calleja, G. (2004) · Advanced Materials · doi:10.1002/adma.200400771 · Cited by 858
Research works printed but not linked: 1
- MalabarbaA FerrariP DepaoliA GalloGG CavalleriB. 1986. Synthesis and conformation of some acetyl derivatives of rifampicin. Farmaco Sci. 41:131–150.
Cited by
Sorted by citations
Items 201–262 of 262
Nanocarrier-mediated CRISPR-Cas delivery: a novel approach against antibiotic-resistant superbugs
Almufarriji, F. M. (2026) · Saudi Pharmaceutical Journal · doi:10.1007/s44446-026-00064-4 · Cited by 5
Dinanti, F. P., Erawati, T., & Hariyadi, D. M. (2024) · International Journal of Drug Delivery Technology · doi:10.25258/ijddt.14.2.77 · Cited by 5
In light-sensitive drug delivery system nanoparticles mediate oxidative stress.
Xiang, W., & Chen, L. (2020) · PubMed Central · Cited by 5
Intracellular Delivery: An Overview
Surve, D. H., Dandekar, P. P., Devarajan, P. V., & Jindal, A. B. (2019) · AAPS advances in the pharmaceutical sciences series · doi:10.1007/978-3-030-29168-6_1 · Cited by 5
Bobbarjang, N., Kumar, L., Dusthackeer, A., & Reddy, Y. P. (2025) · Journal of Pharmaceutical Innovation · doi:10.1007/s12247-025-09971-w · Cited by 4
Mphaphuli, M. T., Sithole, M. N., Kumar, P., Kondiah, P. P. D., Mabrouk, M., & Choonara, Y. E. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.105039 · Cited by 4
Isoniazid Nano-drug Delivery Systems Targeting Macrophages for the Treatment of Tuberculosis
Vemula, S. L., & Gupta, M. T. (2022) · Journal of Preventive Diagnostic and Treatment Strategies in Medicine · doi:10.4103/jpdtsm.jpdtsm_40_22 · Cited by 4
Molecular Switches and Machines with Mechanical Bonds
Bruns, C. J., & Stoddart, J. F. (2016) · Wiley eBooks · doi:10.1002/9781119044123.ch6 · Cited by 4
Toxicity, Safety, and Biodistribution of Multifunctional Mesoporous Silica Nanoparticles
Athalye, M., Patel, R. B., & Patel, M. R. (2021) · Wiley eBooks · doi:10.1002/9781119769897.ch6 · Cited by 4
Ghoderao, P., Sanghavi, S., Bhave, T. M., & Kulkarni, A. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816913-1.00003-9 · Cited by 3
Polymeric and Inorganic Nanoparticles Targeting Chronic Respiratory Diseases
Chan, Y., Ng, S. W., & Soon, L. (2022) · Springer eBooks · doi:10.1007/978-981-16-4392-7_18 · Cited by 3
Al‐Hetty, H. R. A. K., Al-Lami, M. S., Jawad, S. F., Waleed, I., muttashar, H. H., Mohamed, A., Kadhim, M. M., & Derakhshandeh, M. (2022) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2022.10.001 · Cited by 3
Biotechnological Approaches in Infectious Diseases
Banerjee, S., Bose, S., Shukla, A. C., & Baig, M. R. (2024) · Interdisciplinary biotechnological advances · doi:10.1007/978-981-97-1148-2_15 · Cited by 3
Nanomedicines in Tuberculosis: Diagnosis, Therapy and Nanodrug Delivery
Dakkah, A. N., Bataineh, Y. A., Al-Jaidi, B. A., Bayan, M. F., & Nimer, N. A. (2020) · Engineering materials · doi:10.1007/978-3-030-36260-7_13 · Cited by 3
Juyal, V., Kapoor, E., Kumar, V., Ram, V., Tripathi, V., & Bhagat, S. (2014) · Toxicology International · doi:10.4103/0971-6580.128800 · Cited by 3
Therapeutic Applications of Nanobiomaterials
Garg, A. (2017) · IGI Global eBooks · doi:10.4018/978-1-5225-3158-6.ch051 · Cited by 3
Advances in drug delivery systems for intracellular infections: minimizing antibiotic dependency
Wan, Y., Yang, S., Zeng, X., Xie, Y., Peng, L., Luo, J., Xiong, Y., Yang, J., & Duan, P. (2026) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2026.126644 · Cited by 2
Odyniec, M. L., Bell, D. J., Gallant, B. M., Firdaus, R., Ball, G., Hughes, L., Oxtoby, R., Hewitt, B. J., Williams, C. M., Muguruza, A. R., et al. (2026) · JACS Au · doi:10.1021/jacsau.5c01711 · Cited by 2
Metformin for Tuberculosis Infection
Novita, B. D., Muliono, A. C., & Erwin, F. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.99794 · Cited by 2
Application of zinc carbide nanosheet as a promising material for 5-fluorouracil drug delivery
Kadhim, M. M., Rheima, A. M., Alkazazz, F. F., Majdi, A., Hashim, O. A., Al-Jaafari, F. M. D., Umran, D. A., Adel, M., Hachim, S. K., & Zaidan, D. T. (2023) · Inorganic Chemistry Communications · doi:10.1016/j.inoche.2023.110630 · Cited by 2
Yakovtseva, M. N., Kurtova, A. I., Melikov, R. O., Chernov, N., Sizikov, A., Shipunova, V. O., & Nikitin, M. P. (2025) · Nanoscale · doi:10.1039/d5nr00788g · Cited by 2
Ratnaparkhi, M. P., Kamble, O. V., Salvankar, S. S., Shinde, S. R., Kulkarni, G. M., Shewale, A. B., Kadam, D. D., & Shaikh, A. J. (2023) · International Journal of Drug Delivery Technology · doi:10.25258/ijddt.13.3.07 · Cited by 2
Macrophage-Targeted Chemotherapy for Tuberculosis
Shrivastava, P., Gautam, L., Vyas, S., & Vyas, S. P. (2022) · Springer eBooks · doi:10.1007/978-3-030-84164-5_17 · Cited by 2
Arias, S., & Bhatia, S. K. (2015) · SpringerBriefs in public health · doi:10.1007/978-3-319-16775-6_5 · Cited by 2
Formulation Strategies for Antitubercular Drugs by Inhalation
Buttini, F., & Colombo, G. (2016) · Wiley eBooks · doi:10.1002/9781118943182.ch10 · Cited by 2
Jaimes, A. T. C., Poologasundarampillai, G., & Brauer, D. S. (2019) · Wiley eBooks · doi:10.1002/0471238961.koe00050 · Cited by 2
BC3-C3N monolayer for nitrosourea drug delivery: A DFT study
Saadh, M. J., Jasim, S. A., Mahal, A., Ganesan, S., Dhiaa, S. M., Al‐Hussainy, A. F., Verma, R. K., Obaidullah, A. J., & Elawady, A. (2024) · Computational and Theoretical Chemistry · doi:10.1016/j.comptc.2024.114824 · Cited by 1
Almaghrabi, M., Almashhadani, A. Q., Al-Assi, G., Priya, G. P., Ray, S., Pal, A., Sharma, D. R. S. D. R., Usanov, S., Jumanazarov, D., Madaminov, B., et al. (2026) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2026.109149 · Cited by 1
pH, thermo- and stimuli-responsive nanotherapy for tuberculosis
Daisy, E. R. A. C., Vinothini, K., & Rajan, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819985-5.00010-3 · Cited by 1
Application of Nanoemulsion in Tuberculosis Treatment
Singh, S. K., Murti, Y., & Agrawal, N. (2021) · Advances in chemical and materials engineering book series · doi:10.4018/978-1-7998-8378-4.ch008 · Cited by 1
Nanotechnology-Based Vaccination for TB
Barik, A., & Dey, S. (2023) · Springer eBooks · doi:10.1007/978-3-031-20521-7_7 · Cited by 1
Therapeutic potential of nano assisted delivery in tuberculosis and its management
Singh, R., Jadhav, K., Jhilta, A., & Verma, R. K. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13337-4.00019-7 · Cited by 1
Silica Nanoparticle for the Treatment of Bacterial Infections
Das, C., Chakraborty, D., & Mondal, N. K. (2024) · Springer eBooks · doi:10.1007/978-3-031-63961-6_3 · Cited by 1
Nanomaterials for Selective Targeting of Intracellular Pathogens
Syed, M. A., & Ali, N. (2019) · Springer eBooks · doi:10.1007/978-3-030-29768-8_6 · Cited by 1
Delivery of Drug Payloads to Organs and Organ-Systems
Pang, S.-W., Soon, M. L.-K., Shameli, K., Pushpamalar, J., & Teow, S. (2021) · Nanotechnology in the life sciences · doi:10.1007/978-3-030-61021-0_11 · Cited by 1
Basics of Targeted Drug Delivery
Doshi, K. A. (2022) · Methods and principles in medicinal chemistry · doi:10.1002/9783527827855.ch1 · Cited by 1
Therapeutic Applications of Nanobiomaterials
Garg, A. (2016) · Advances in medical technologies and clinical practice book series · doi:10.4018/978-1-5225-0751-2.ch015
David, M., Florescu, M., Barsan, M. M., Ţugulea, L., & Brett, C. M. A. (2014) · Digital library - University of Pardubice (University of Pardubice)
Management of Ocular Tuberculosis
Kumar, N., Anthony, E., Majumder, P. D., Kharel, R., & Biswas, J. (2017) · Essentials in ophthalmology/Essentials ophthalmology · doi:10.1007/978-3-319-57520-9_6
Nanomedicine progress in prevention, detection, and treatment of tuberculosis
Marutescu, L. G., Frăţiean, D., & Chifiriuc, M. C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816505-8.00011-4
Approaches toward designing nanocarriers for tuberculosis drug delivery
Mehnath, S., & Jeyaraj, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819985-5.00012-7
Niu, N., Shi, Z., Yang, Z., Li, Y., Shi, J.-D., Wang, Z., Liu, H., Ma, X.-M., & ding, H. (2020) · doi:10.21203/rs.3.rs-36126/v1
Yang, Z., Niu, N., Lou, C., Wang, X., Wang, C., & Shi, Z. (2022) · Research Square · doi:10.21203/rs.3.rs-1223038/v1
Drug Delivery using Nano-Material based Enzymes
Mujahid, F. (2022) · Materials research foundations · doi:10.21741/9781644901977-7
Srivastav, Y., Prajapati, A., & Kumar, M. (2023) · International Journal of Pharmaceutical Sciences Review and Research · doi:10.47583/ijpsrr.2023.v82i02.012
BSA nanoclusters-based sensor for detection of dopamine in schizophrenia from biofluids
Khanolkar, B., & Shende, P. K. (2024) · Drug Development and Industrial Pharmacy · doi:10.1080/03639045.2024.2328722
The design for drug delivery using pili in Mycobacterium tuberculosis
Ghanavi, J., Farnia, P., Aghajani, J., Ayoubi, S., Besharati, S., Farnia, P., & Velayati, A. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-21712-8.00020-x
Bobbarjang, N., Padmanabha Reddy, Y., Dusthackeer, A., & Kumar, L. (2025) · Research Square · doi:10.21203/rs.3.rs-6422681/v1
Gupta, Y. D., Sarkar, R., Bhowmik, A., Bag, N., Hajra, S., Das, S., & Bhandary, S. (2025) · Nanoscience & Nanotechnology-Asia · doi:10.2174/0122106812373327250509094328
Paliwal, H., Kapoor, D. U., Prajapati, B. G., Paul, P. K., & Srichana, T. (2026) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2026.108184
Advantages of targeted nanomedicine in cancer treatment
Misra, S. K., & Pathak, K. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44579-8.00008-4
Nanomedicinas a base de productos naturales para el tratamiento de la tuberculosis
Armendáriz-Barragán, B. (2018) · doi:10.70675/08d21285zf933z4ea7z89f7z17801f6cd4ec
Shubha, B. N., Kumar, L., Dusthackeer, A., & Reddy, Y. P. (2026) · Biomedical Materials & Devices · doi:10.1007/s44174-026-00702-4
Makiabadi, B., Naderi, F., Zakarianezhad, M., & Raessi, A. (2026) · Nanoscale Advances · doi:10.1039/d5na01168j
A rifampin-loaded porous bioceramic box as a drug delivery system for spinal tuberculosis
Guan, J., Ye, J., Hu, G., Hu, Y., Ma, H., & Zhu, L. (2026) · Letters in Drug Design & Discovery · doi:10.1016/j.lddd.2026.100442
Harnessing Inhaled Nanoparticles for Enhanced Pharmacokinetics and Pharmacodynamics of Drugs
Arun, B., Matcha, S., & Rao, G. G. (2026) · Royal Society of Chemistry eBooks · doi:10.1039/9781837676439-00250
Inorganic Nanoparticle-Based Theranostics for Pulmonary Diseases
Yadav, B., Poojary, S., & Dash, A. K. (2026) · Journal of Nanotheranostics · doi:10.3390/jnt7030021
Martinena, C. B., Ortellado, F. G., Vitti, A. D., Martin, C., Bouyrie, A. J. B., Bernabeu, E., Zuazo, R., Chiappetta, D. A., García, V., Amiano, N. O., et al. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18101279
Abdulkarim, M. M., Fattah, F. H., Hamasaeed, A. G., Anwar, K. A., Ezzat, S. L., Mustafa, A. M., Mohammed, K. K., Mohammed, S. H., Mahmood, Z. F., Mohammed, R. A., et al. (2026) · Journal of Applied Microbiology · doi:10.1093/jambio/lxag268
Metadata
- 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
- 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
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
