Biosensors and Nanotheranostics
Bionanotechnology, Drug Delivery, Therapeutics | online ISSN 3064-7789
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Volume 5 Number 1 2026
REVIEWS (Open Access)
Inhalable Nanoparticle Theranostics for Targeted Delivery and Imaging in Multidrug-Resistant Tuberculosis
Roya Mirzaei 1*, Mansoureh Nazari V. 2
Biosensors and Nanotheranostics 5 (1) 1-8 https://doi.org/10.25163/biosensors.5110989
Submitted: 14 May 2026 Revised: 02 July 2026 Accepted: 11 July 2026 Published: 13 July 2026
Abstract
Multidrug-resistant tuberculosis (MDR-TB) continues to outpace the tools built to contain it. Standard regimens are long, toxic, and only intermittently curative, and much of that failure traces to a problem of access: systemically delivered antibiotics rarely reach the bacilli sheltered inside alveolar macrophages or buried within the hypoxic, avascular core of the tuberculous granuloma. This review synthesizes how inhalable nanoparticle theranostics are being engineered to close that gap. We examine four linked domains. First, aerosol formulation engineering, where lipid, polymeric, and inorganic carriers are tuned to a mass median aerodynamic diameter of 1–5 µm so that payloads settle in the deep alveoli rather than the oropharynx (Second, active receptor-mediated targeting, in which ligands such as mannose, β-glucan, and hyaluronic acid exploit CD206, Dectin-1, and CD44 to drive nanocarriers into the intracellular niche of Mycobacterium tuberculosis. Third, integrated diagnostics, where near-infrared luminogens, iron-based contrast agents, and biomimetic coatings allow drug deposition and bacterial clearance to be watched in situ. Fourth, host-directed and light-activated modalities that act independently of bacterial genotype, including autophagy induction, macrophage repolarization, and photothermal killing. Across these domains the preclinical signal is consistent and often striking, yet translation remains constrained by nanotoxicity, aerosol instability, surfactant-corona effects, and manufacturing hurdles. We argue that the field's near-term value lies less in any single nanomaterial than in the convergence of localized delivery, imaging, and resistance-agnostic action within one construct.
Keywords: multidrug-resistant tuberculosis; inhalable nanomedicine; theranostics; alveolar macrophage targeting; granuloma; host-directed therapy; near-infrared imaging
References
Afreen, N., Begum, M. S., & Sharma, S. (2026). Nanotechnology-based novel approaches for the treatment of tuberculosis. Next Nanotechnology, 9, Article 100411. https://doi.org/10.1016/j.nxnano.2026.100411
Akinnawo, C. A., & Dube, A. (2025). Clinically relevant metallic nanoparticles in tuberculosis diagnosis and therapy. Advanced Therapeutics, 8(1), Article 2400189. https://doi.org/10.1002/adtp.202400189
Bahlool, A. Z., Fattah, S., O'Sullivan, A., Cavanagh, B., MacLoughlin, R., Keane, J., O'Sullivan, M. P., & Cryan, S. A. (2022). Development of inhalable ATRA-loaded PLGA nanoparticles as host-directed immunotherapy against tuberculosis. Pharmaceutics, 14(8), 1745. https://doi.org/10.3390/pharmaceutics14081745
Baranyai, Z., Soria-Carrera, H., Alleva, M., Millán-Placer, A. C., Lucía, A., Martín-Rapún, R., Aínsa, J. A., & de la Fuente, J. M. (2021). Nanotechnology-based targeted drug delivery: An emerging tool to overcome tuberculosis. Advanced Therapeutics, 4(1), Article 2000113. https://doi.org/10.1002/adtp.202000113
Bekale, R. B., Maphasa, R. E., D'Souza, S., Hsu, N. J., Walters, A., Okugbeni, N., Kinnear, C., Jacobs, M., Sampson, S. L., Meyer, M., Morse, G. D., & Dube, A. (2025). Immunomodulatory nanoparticles induce autophagy in macrophages and reduce Mycobacterium tuberculosis burden in the lungs of mice. ACS Infectious Diseases, 11(3), 610–625. https://doi.org/10.1021/acsinfecdis.4c00713
Bera, H., Zhao, C., Tian, X., Cun, D., & Yang, M. (2024). Mannose-decorated solid-lipid nanoparticles for alveolar macrophage targeted delivery of rifampicin. Pharmaceutics, 16(3), Article 429. https://doi.org/10.3390/pharmaceutics16030429
Bourguignon, T., Godinez-Leon, J. A., & Gref, R. (2023). Nanosized drug delivery systems to fight tuberculosis. Pharmaceutics, 15(2), Article 393. https://doi.org/10.3390/pharmaceutics15020393
Bueno, J. (2025). Nanotheranostic applications in pulmonary infections. Academic Medicine & Health, 2025, Article 7934. https://doi.org/10.20935/AcadMedHealth7934
Carnero, M., Meurer, M., Goethe, R., Singh, M., Reljic, R., & von Köckritz-Blickwede, M. (2026). Nanomaterials for pulmonary drug delivery and targeted tuberculosis therapy. Advanced Healthcare Materials, 15(14), Article 2503964. https://doi.org/10.1002/adhm.202503964
Clemens, D. L., Lee, B.-Y., Xue, M., Thomas, C. R., Meng, H., Ferris, D., Nel, A. E., Zink, J. I., & Horwitz, M. A. (2012). Targeted intracellular delivery of antituberculosis drugs to Mycobacterium tuberculosis-infected macrophages via functionalized mesoporous silica nanoparticles. Antimicrobial Agents and Chemotherapy, 56(5), 2535–2545. https://doi.org/10.1128/AAC.06049-11
Cung, J., Husni, P., & Oh, K. T. (2025). Actively targeted nanoparticles for enhanced diagnosis, treatment, and vaccination of tuberculosis: A systematic review. International Journal of Nanomedicine, 20, 14343–14374. https://doi.org/10.2147/IJN.S557784
Datta, M., Via, L. E., Dartois, V., Weiner, D. M., Zimmerman, M., Kaya, F., Walker, A. M., Fleegle, J. D., Raplee, I. D., McNinch, C., & Jain, R. K. (2024). Normalizing granuloma vasculature and matrix improves drug delivery and reduces bacterial burden in tuberculosis-infected rabbits. Proceedings of the National Academy of Sciences, 121(12), Article e2321336121. https://doi.org/10.1073/pnas.2321336121
Erothi, S., et al. (2026). Inhalable nanoparticle delivery targeting alveolar macrophages for the treatment of pulmonary tuberculosis: A structural gap analysis. World Journal of Pharmacy and Pharmaceutical Sciences, 15(10), 35–42.
Fan, S., Zhao, D., Wang, J., et al. (2024). Photothermal and host immune activated therapy of cutaneous tuberculosis using macrophage targeted mesoporous polydopamine nanoparticles. Materials Today Bio, 28, Article 101232. https://doi.org/10.1016/j.mtbio.2024.101232
Gao, Y., Wang, W., Yue, X., et al. (2025). Inhalable nanoparticle-based delivery systems for the treatment of pulmonary infections: Status quo and barrier-overcoming strategies. Drug Delivery, 32(1), Article 2544683. https://doi.org/10.1080/10717544.2025.2544683
Garg, T., Rath, G., & Goyal, A. K. (2016). Inhalable chitosan nanoparticles as antitubercular drug carriers for an effective treatment of tuberculosis. Artificial Cells, Nanomedicine, and Biotechnology, 44(3), 997–1001. https://doi.org/10.3109/21691401.2015.1008508
Gautam, S., & Venugopal, D. (2026). Nanomaterials for active, latent, and multidrug-resistant tuberculosis diagnostics. In Nanodiagnostics to Identify and Detect Microbial Infections and Antimicrobial Resistance (pp. 185–200). Academic Press. https://doi.org/10.1016/B978-0-443-33072-8.00017-0
Gupta, P. K., Jahagirdar, P., Tripathi, D., Devarajan, P. V., & Kulkarni, S. (2023). Macrophage targeted polymeric curcumin nanoparticles limit intracellular survival of Mycobacterium tuberculosis through induction of autophagy and augment anti-TB activity of isoniazid in RAW 264.7 macrophages. Frontiers in Immunology, 14, Article 1233630. https://doi.org/10.3389/fimmu.2023.1233630
Jia, Y., et al. (2022). Hyaluronic acid-coated chitooligosaccharide nanoparticles for targeting macrophages in bacterial infections. International Journal of Pharmaceutics: X, 4, Article 100574.
Kaur, I. P., & Singh, H. (2014). Nanostructured drug delivery for better management of tuberculosis. Journal of Controlled Release, 184, 36–50. https://doi.org/10.1016/j.jconrel.2014.03.048
Kia, P., Ruman, U., Pratiwi, A. R., & Hussein, M. Z. (2023). Innovative therapeutic approaches based on nanotechnology for the treatment and management of tuberculosis. International Journal of Nanomedicine, 18, 1159–1191. https://doi.org/10.2147/IJN.S364634
Kutscher, H. L., et al. (2026). Repeated pulmonary dosing of beta-glucan-chitosan-PLGA nanoparticles controls Mycobacterium tuberculosis in mice. Antimicrobial Agents and Chemotherapy, 70(2), Article e0148025. https://doi.org/10.1128/aac.0148025
Li, B., Wang, W., Zhao, L., Wu, Y., Li, X., Yan, D., Gao, Q., Yan, Y., Zhang, J., Feng, Y., & Zhang, H. (2024). Photothermal therapy of tuberculosis using targeting pre-activated macrophage membrane-coated nanoparticles. Nature Nanotechnology, 19(6), 834–845. https://doi.org/10.1038/s41565-024-01618-0
Liao, Y., Li, B., Zhao, Z., Fu, Y., Tan, Q., Li, X., Wang, W., Yin, J., Shan, H., Tang, B. Z., & Zhang, X. (2020). Targeted theranostics for tuberculosis: A rifampicin-loaded aggregation-induced emission carrier for granulomas tracking and anti-infection. ACS Nano, 14(7), 8046–8058. https://doi.org/10.1021/acsnano.0c03014
Lin, W., et al. (2024). Zinc oxide hybrid selenium nanoparticles promote apoptosis and autophagy in BCG-infected macrophages via PI3K/Akt/mTOR pathway inhibition. Microbial Pathogenesis, 180, Article 106132. https://doi.org/10.1016/j.micpath.2023.106132
Luan, H., Peng, C., Yasin, P., Shang, Q., Xiang, W., & Song, X. (2025). Mannosamine-engineered nanoparticles for precision rifapentine delivery to macrophages: Advancing targeted therapy against Mycobacterium tuberculosis. Drug Design, Development and Therapy, 19, 2081–2102. https://doi.org/10.2147/DDDT.S505682
Luz, I. E., Stewart, I. E., Mortensen, N. P., & Hickey, A. J. (2020). Designing inhalable metal organic frameworks for pulmonary tuberculosis treatment and theragnostics via spray drying. Chemical Communications, 56(87), 13339–13342. https://doi.org/10.1039/d0cc05471b
Lyu, J., et al. (2024). Understanding the development of tuberculous granulomas: Insights into host protection and pathogenesis. Frontiers in Immunology, 15, Article 1427559. https://doi.org/10.3389/fimmu.2024.1427559
Makled, S., Boraie, N., & Nafee, N. (2021). Nanoparticle-mediated macrophage targeting—a new inhalation therapy tackling tuberculosis. Drug Delivery and Translational Research, 11(3), 1037–1055. https://doi.org/10.1007/s13346-020-00849-7
Muthukrishnan, L. (2021). Multidrug resistant tuberculosis—diagnostic challenges and its conquering by nanotechnology approach—an overview. Chemico-Biological Interactions, 337, Article 109397. https://doi.org/10.1016/j.cbi.2021.109397
Omoteso, O. A., Fadaka, A. O., Walker, R. B., & Khamanga, S. M. (2025). Innovative strategies for combating multidrug-resistant tuberculosis: Advances in drug delivery systems and treatment. Microorganisms, 13(4), Article 722. https://doi.org/10.3390/microorganisms13040722
Onnainty, R., & Granero, G. E. (2025). Advancements in nanotheranostic approaches for tuberculosis: Bridging diagnosis, prevention, and therapy through smart nanoparticles. Journal of Nanotheranostics, 6(4), Article 33. https://doi.org/10.3390/jnt6040033
Poojary, S., & Dash, A. (2025). Inorganic theranostic nanoparticles for pulmonary delivery: Translational perspectives and safety considerations. Journal of Nanotheranostics, 7(1), Article 21. https://doi.org/10.3390/jnt7010021
Prideaux, B., Via, L. E., Zimmerman, M. D., et al. (2015). The association between sterilizing activity and drug distribution into tuberculosis lesions. Nature Medicine, 21(10), 1223–1227. https://doi.org/10.1038/nm.3937
Ramachandran, S., Prakash, P., Mohtar, N., Kumar, K. S., & Parumasivam, T. (2023). Review of inhalable nanoparticles for the pulmonary delivery of anti-tuberculosis drugs. Pharmaceutical Development and Technology, 28(10), 1083–1095. https://doi.org/10.1080/10837450.2023.2279691
Ranjith Singh, S., Makatini, M. M., Marimuthu, T., & Choonara, Y. E. (2025). Advancing tuberculosis chemotherapy: Targeted nanomedicines for the Mycobacterium TB granuloma. Small, 21(49), Article e06381. https://doi.org/10.1002/smll.202506381
Rudolph, D., Redinger, N., Schwarz, K., Li, F., Hädrich, G., Cohrs, M., Dailey, L. A., Schaible, U. E., & Feldmann, C. (2023). Amorphous drug nanoparticles for inhalation therapy of multidrug-resistant tuberculosis. ACS Nano, 17(10), 9478–9486. https://doi.org/10.1021/acsnano.3c01664
Shah, S., Cristopher, D., Sharma, S., Soniwala, M., & Chavda, J. (2020). Inhalable linezolid loaded PLGA nanoparticles for treatment of tuberculosis: Design, development and in vitro evaluation. Journal of Drug Delivery Science and Technology, 60, Article 102013. https://doi.org/10.1016/j.jddst.2020.102013
Sharma, D., et al. (2025). Integrated nanomedicine, gene editing, and host-directed therapy for personalized tuberculosis management. Pharmaceutics, 17(10), Article 1459. https://doi.org/10.3390/pharmaceutics17101459
Shen, L., Liao, K., Yang, E., Yang, F., Lin, W., Wang, J., Fan, S., Huang, X., Chen, L., Shen, H., et al. (2023). Macrophage targeted iron oxide nanodecoys augment innate immunological and drug killings for more effective Mycobacterium tuberculosis clearance. Journal of Nanobiotechnology, 21, Article 369. https://doi.org/10.1186/s12951-023-02132-w
Tiwari, P. K., Verma, D., Shivani, Singh, M., Kushwaha, D., & Kushwaha, A. K. (2026). Nanomedicine-based drug delivery systems for tuberculosis: Overcoming resistance, dormancy, and translational barriers. Next Nanotechnology, 10, Article 100642. https://doi.org/10.1016/j.nxnano.2026.100642
Uskokovic, V. (2023). Lessons from the history of inorganic nanoparticles for inhalable diagnostics and therapeutics. Advances in Colloid and Interface Science, 315, Article 102903. https://doi.org/10.1016/j.cis.2023.102903
Wang, H., Li, B., Sun, Y., Ma, Q., Feng, Y., Jia, Y., Wang, W., Su, M., Liu, X., Shu, B., et al. (2024). NIR-II AIE luminogen-based erythrocyte-like nanoparticles with granuloma-targeting and self-oxygenation characteristics for combined phototherapy of tuberculosis. Advanced Materials, 36(41), Article e2406143. https://doi.org/10.1002/adma.202406143
Wang, Y., Liu, Y., Long, M., Dong, Y., Li, L., & Zhou, X. (2024). Nanoparticles target M2 macrophages to silence kallikrein-related peptidase 12 for the treatment of tuberculosis and drug-resistant tuberculosis. Acta Biomaterialia, 188, 358–373. https://doi.org/10.1016/j.actbio.2024.08.012
World Health Organization. (2024). Global tuberculosis report 2024. World Health Organization.
Wyszogrodzka, G., Dorozynski, P., Gil, B., Roth, W. J., Strzempek, M., Marszalek, B., Weglarz, W. P., Menaszek, E., Strzempek, W., & Kulinowski, P. (2018). Iron-based metal-organic frameworks as a theranostic carrier for local tuberculosis therapy. Pharmaceutical Research, 35(7), Article 144. https://doi.org/10.1007/s11095-018-2427-0
Zhu, X., et al. (2026). Nanodrug delivery systems for lower respiratory tract infections. International Journal of Nanomedicine, 21, Article 623071. https://doi.org/10.2147/IJN.S623071