Advances in Mesoporous Silica Nanoparticles for Targeted and Controlled Drug Delivery
Abstract
Mesoporous Silica Nanoparticles (MSNs) have emerged as a versatile and highly tunable platform for controlled and targeted therapeutic applications. Their unique structural features including high surface area, tunable pore size, adjustable morphology, and abundant surface silanol groups enable efficient drug loading, precise surface functionalization, and stimuli-responsive release. Advances in synthesis methods, including sol-gel, soft-template, hard-template, and microemulsion approaches, allow precise control over particle size, pore architecture, and surface properties, which are critical for optimizing biological performance. Surface functionalization strategies, such as post-synthesis grafting, co-condensation, polymer coating, and ligand conjugation, enhance biocompatibility, targeting efficiency, and controlled drug release, while minimizing premature drug leakage and systemic toxicity. MSNs support diverse drug loading mechanisms, including physical adsorption, covalent attachment, and encapsulation with pore capping, enabling sustained and stimuli-responsive therapeutic release in response to pH, redox potential, enzymes, or external triggers. Targeting strategies, encompassing passive accumulation, active ligand-mediated targeting, biomimetic coatings, and organelle-specific delivery, further enhance therapeutic specificity and efficacy. Despite these advances, challenges remain in clinical translation, including long-term toxicity, immunogenicity, and large-scale reproducible synthesis. Future research is expected to focus on multifunctional, stimuli-responsive, and theragnostic MSNs that integrate combination therapies, biomimetic targeting, and real-time monitoring, thereby advancing personalized and precision medicine. This review provides a comprehensive overview of MSN structure, synthesis, functionalization, drug loading, targeting strategies, and future perspectives, highlighting their potential as next-generation nanotherapeutic platforms.
Keywords:
Mesoporous silica nanoparticles, Controlled drug delivery, Targeted therapeutics, Surface functionalization, Stimuli-responsive release, NanomedicineReferences
- [1] Saha, A., Mishra, P., Biswas, G., & Bhakta, S. (2024). Greening the pathways: a comprehensive review of sustainable synthesis strategies for silica nanoparticles and their diverse applications. RSC advances, 14(16), 11197–11216. https://doi.org/10.1039/D4RA01047G
- [2] Ostapchuk, G. O. (2024). Eco-friendly synthesis of silica nanoparticles and their applications. Materials research foundations. https://doi.org/10.21741/9781644903261-1
- [3] Ibrahim, S. S., Elbehery, H. H., & Samy, A. (2024). The efficacy of green silica nanoparticles synthesized from rice straw in the management of Callosobruchus maculatus (Col., Bruchidae). Scientific reports, 14(1), 8834. https://doi.org/10.1038/s41598-024-58856-4
- [4] Wei, L., Fan, Y., Lin, H., & Che, S. (2024). Synthesis of Anisotropic Silica Nanoparticles. Chemical research in chinese universities, 40(6), 1220–1226. https://doi.org/10.1007/s40242-024-4092-7
- [5] Song, X., Segura-Egea, J. J., & Díaz-Cuenca, A. (2023). Sol–Gel technologies to obtain advanced bioceramics for dental therapeutics. Molecules, 28(19), 1-27. https://doi.org/10.3390/molecules28196967
- [6] Wang, Y., Li, Z., Ouyang, J., & Karniadakis, G. E. (2020). Controlled release of entrapped nanoparticles from thermoresponsive hydrogels with tunable network characteristics. Soft matter, 16(20), 4756–4766. https://doi.org/10.1039/D0SM00207K
- [7] Zhou, X., Liu, Y., Huang, Y., Ma, Y., Lv, J., & Xiao, B. (2019). Mucus-penetrating polymeric nanoparticles for oral delivery of curcumin to inflamed colon tissue. Journal of drug delivery science and technology, 52, 157–164. https://doi.org/10.1016/j.jddst.2019.04.030
- [8] Zaid Alkilani, A., McCrudden, M. T., & Donnelly, R. F. (2015). Transdermal drug delivery: Innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics, 7(4), 438–470. https://doi.org/10.3390/pharmaceutics7040438
- [9] Piconi, C., & Sprio, S. (2021). Oxide bioceramic composites in orthopedics and dentistry. Journal of composites science, 5(8), 1-13. https://doi.org/10.3390/jcs5080206
- [10] Tapeh, S. M. T., Baei, M. S., & Keshel, S. H. (2021). Synthesis of thermogel modified with biomaterials as carrier for hUSSCs differentiation into cardiac cells: Physicomechanical and biological assessment. Materials science and engineering: c, 119, 111517. https://doi.org/10.1016/j.msec.2020.111517
- [11] Zafar, M. J., Zhu, D., & Zhang, Z. (2019). 3D Printing of Bioceramics for bone tissue engineering. Materials, 12(20), 1–26. https://doi.org/10.3390/ma12203361
- [12] Blatt, S., Thiem, D. G., Kyyak, S., Pabst, A., Al-Nawas, B., & Kämmerer, P. W. (2021). Possible implications for improved osteogenesis? The combination of platelet-rich fibrin with different bone substitute materials. Frontiers in bioengineering and biotechnology, 9, 1-12. https://doi.org/10.3389/fbioe.2021.640053
- [13] Elshazly, N., Nasr, F. E., Hamdy, A., Saied, S., & Elshazly, M. (2024). Advances in clinical applications of bioceramics in the new regenerative medicine era. World journal of clinical cases, 12(11), 1863–1869. https://doi.org/10.12998/wjcc.v12.i11.1863
- [14] Naghib, S. M., Amiri, S., & Mozafari, M. R. (2024). Stimuli-responsive chitosan-based nanocarriers for drug delivery in wound dressing applications: A review. Carbohydrate polymer technologies and applications, 7, 100497. https://doi.org/10.1016/j.carpta.2024.100497
- [15] Safarzadeh, S., Mozafari, M. R., & Naghib, S. M. (2024). Chitosan-incorporated bioceramic-based nanomaterials for localized release of therapeutics and bone regeneration: An overview of recent advances and progresses. Current organic chemistry, 28(15), 1190–1214. https://doi.org/10.2174/0113852728304647240426201554
- [16] Wang, X., Xiao, Y., Song, W., Ye, L., Yang, C., Xing, Y., & Yuan, Z. (2023). Clinical application of calcium silicate-based bioceramics in endodontics. Journal of translational medicine, 21(1), 1–16. https://doi.org/10.1186/s12967-023-04550-4
- [17] Vaiani, L., Boccaccio, A., Uva, A. E., Palumbo, G., Piccininni, A., Guglielmi, P., … ., & Ballini, A. (2023). Ceramic materials for biomedical applications: An overview on properties and fabrication processes. Journal of functional biomaterials, 14(13), 1-22. https://doi.org/10.3390/jfb14030146
- [18] Rezwan, K., Chen, Q. Z., Blaker, J. J., & Boccaccini, A. R. (2006). Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials, 27(18), 3413–3431. https://doi.org/10.1016/j.biomaterials.2006.01.039
- [19] Mousavi, A., & Yaghoobi, H. (2025). Ethical challenges of personalized medicine. The second international congress on artificial intelligence in medical sciences, Tehran, Iran. Civilica. (In Persian). https://civilica.com/doc/2310901
- [20] Wiwanitkit, V. (2017). Ethics in nanomedicine: A concern on new nanotechnology. Med One, 2(5), e170025. https://doi.org/10.20900/mo.20170025
- [21] Ma, F. X., Achagri, G., Zhou, L. C., Hao, B., & Ma, P. C. (2024). Enhanced performance of polyurethane foam with presence of silica nanoparticles. Composites communications, 46, 101841. https://doi.org/10.1016/j.coco.2024.101841
- [22] Syed, J., Hakkim, N. L., Nebhani, L., & Gosvami, N. N. (2024). Enhancing tribological properties of lubricated contacts via synergistic interactions of green silica nanoparticles and ZDDP. Tribology international, 197, 109829. https://doi.org/10.1016/j.triboint.2024.109829
- [23] Majidi, R. F., Mesgar, A. S. M., & Milan, P. B. (2024). Surface-modified, zinc-incorporated mesoporous silica nanoparticles with improved antibacterial and rapid hemostatic properties. Colloids and surfaces b: Biointerfaces, 243, 114132. https://doi.org/10.1016/j.colsurfb.2024.114132
- [24] Nuti, S., Fernández-Lodeiro, A., Galhano, J., Oliveira, E., Duarte, M. P., Capelo-Martínez, J. L., … ., & Fernández-Lodeiro, J. (2024). Tailoring mesoporous silica-coated silver nanoparticles and polyurethane-doped films for enhanced antimicrobial applications. Nanomaterials, 14(5), 1-12. https://doi.org/10.3390/nano14050462
- [25] Yu, J., Dan, N., Eslami, S. M., & Lu, X. (2024). State of the art of silica nanoparticles: An overview on biodistribution and preclinical toxicity studies. The AAPS journal, 26(3), 35. https://doi.org/10.1208/s12248-024-00906-w
- [26] Mathur, J., & Goswami, P. (2024). Positive impact of green synthesized silica nanoparticles in plant growth promotion and physiological responses of eruca sativa mill. Journal of soil science and plant nutrition, 24(2), 2263–2275. https://doi.org/10.1007/s42729-024-01725-w
- [27] Lu, J., Mei, M., & Huang, C. (2025). Influence of silicon dioxide nanoparticles on hydrophobicity and transparency of polydimethylsiloxanes coatings hybridized with silicon dioxide nanoparticles. Thin solid films, 828, 140800. https://doi.org/10.1016/j.tsf.2025.140800
- [28] Niknejad, K., Sharifzadeh Baei, M., & Motallebi Tala Tapeh, S. (2018). Synthesis of metformin hydrochloride nanoliposomes: Evaluation of physicochemical characteristics and release kinetics. International journal of nano dimension, 9(3), 298–313. https://dorl.net/dor/20.1001.1.20088868.2018.9.3.9.7
- [29] Fazelinejad, A., Behbahani, M., & Harsij, Z. (2024). Utilization of silicon dioxide nanoparticles and silicon salts to enhance astaxanthin production in Haematococcus Pluvialis. Algal research, 82, 103633. https://doi.org/10.1016/j.algal.2024.103633
- [30] Hameed, W. A., & Abbas, M. N. (2024). Dyes adsorption from contaminated aqueous solution using SiO2 nanoparticles prepared from extracted tree leaves. Journal of ecological engineering, 25(7), 41-57. http://dx.doi.org/10.12911/22998993/187921