Bionanotechnology, Drug Delivery, Therapeutics | online ISSN 3064-7789
RESEARCH ARTICLE   (Open Access)

Development of Stimuli-Responsive Mesoporous Silica Nanoparticles for Targeted Cancer Drug Delivery: Synthesis, Characterization, and Ion Incorporation

Klepetsanis Pavlos 1*

+ Author Affiliations

Biosensors and Nanotheranostics 1(1) 1-9 https://doi.org/10.25163/biosensors.119852

Submitted: 04 October 2022  Revised: 10 December 2022  Published: 15 December 2022 

This research advances cancer drug delivery using mesoporous silica nanoparticles, offering precise, stimuli-responsive, and biocompatible therapeutic solutions.

Abstract


Background: The rising incidence of breast cancer has heightened the need for advanced drug delivery systems. Mesoporous silica nanoparticles (MSNs) have emerged as a promising carrier for targeted cancer therapy due to their biocompatibility and ability to provide controlled drug release. Their functionalization, size, and shape allow for enhanced internalization and accumulation in tumors, reducing adverse effects and improving efficacy. Methods: MSNs were synthesized using the sol-gel process with tetraethyl orthosilicate (TEOS) as a precursor. The effects of variables such as pH, stirring rates, and the use of catalysts were studied to optimize particle size and morphology. Zinc and cerium ions were incorporated into the MSN network via post-grafting to enhance therapeutic efficacy. Particles were characterized using FT-IR, XRD, and TEM to analyze size, crystallinity, and composition. Additionally, degradation studies were performed in a physiological medium.  Results: Monodispersed MSNs of less than 200 nm were successfully synthesized, with optimal properties achieved at a stirring rate of 600 rpm and pH between 10.5 and 11.5. Zinc and cerium incorporation resulted in enhanced ROS generation, potentially increasing the cytotoxicity towards cancer cells. Zinc showed increased release in acidic environments, while cerium exhibited pro-oxidant activity in cancer microenvironments. Characterization confirmed successful ion incorporation, with particle sizes maintained below 200 nm. Conclusion: The optimized MSNs with zinc and cerium incorporation demonstrated potential for targeted cancer therapy by inducing oxidative stress in cancer cells while offering controlled drug release. This study highlights the potential of MSNs as a versatile drug delivery platform for oncology.

Keywords: Mesoporous Silica Nanoparticles (MSNs), Stimuli-responsive drug delivery, Cancer therapy, Zinc and cerium ions, Sol-gel synthesis

References


Ahamed, M., Javed Akhtar, M., Kumar, S., Khan, M. I., Ahmad, A., & Alrokayan, S. A. (2012). Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species. International Journal of Nanomedicine, 7, 845-857. https://doi.org/10.2147/IJN.S29511

Bogdan, J., Plawinska-Czarnak, J., & Zarzynska, J. (2017). Nanoparticles of titanium and zinc oxides as novel agents in tumor treatment: A review. Nanoscale Research Letters, 12(1), 41. https://doi.org/10.1186/s11671-017-1725-6

Chen, X., Brauer, D. S., & Karpukhina, N. (2014). ‘Smart’ acid-degradable zinc-releasing silicate glasses. Materials Letters, 126, 278-280. https://doi.org/10.1016/j.matlet.2014.03.052

Du, J., Lane, L., & Nie, S. (2015). Stimuli-responsive nanoparticles for targeting the tumor microenvironment. Journal of Controlled Release, 219, 205-214. https://doi.org/10.1016/j.jconrel.2015.07.018

Du, X., & He, J. (2011). Spherical silica micro/nanomaterials with hierarchical structures: Synthesis and applications. Nanoscale, 3(10), 3984-3996. https://doi.org/10.1039/C1NR10772J

Ertl, G., Knözinger, H., & Weitkamp, J. (1999). Preparation of solid catalysts. (1st ed.). Weinheim: Wiley-VCH.

Highsmith, J. (2014). Nanoparticles in Biotechnology, Drug Development & Drug Delivery (BIO113B). BCC Research.

Huang, X., Teng, X., Chen, D., Tang, F., & He, J. (2010). The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function. Biomaterials, 31(3), 438-448. https://doi.org/10.1016/j.biomaterials.2009.10.047

Innocenzi, P. (2016). The sol to gel transition (1st ed., pp. 12-17). The Sol to Gel Transition.

Jones, J. R. (2013). Review of bioactive glass: From Hench to hybrids. Acta Biomaterialia, 9(1), 4457-4486. https://doi.org/10.1016/j.actbio.2012.09.023

Kim, K., & Kim, H. (2003). Comparison of the effect of reaction parameters on particle size in the formation of SiO2 ,and ZrO2  nanoparticles. Materials Letters, 57(21), 3211-3216. https://doi.org/10.1016/S0167-577X(03)00216-5

Kim, T., Chung, P., & Lin, V. (2010). Facile synthesis of monodisperse spherical MCM-48 mesoporous silica nanoparticles with controlled particle size. Chemistry of Materials, 22(17), 5093-5104. https://doi.org/10.1021/cm100489e

Korsvik, C., Patil, S., Seal, S., & Self, W. (2007). Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chemical Communications, (10), 1056-1058. https://doi.org/10.1039/b616496j

Labbaf, S., Tsigkou, O., Müller, K., Stevens, M., Porter, A., & Jones, J. R. (2011). Spherical bioactive glass particles and their interaction with human mesenchymal stem cells in vitro. Biomaterials, 32(4), 1010-1018. https://doi.org/10.1016/j.biomaterials.2010.10.049

Liang, M. K., Limo, M. J., Sola-Rabada, A., Roe, M. J., & Perry, C. C. (2014). New insights into the mechanism of ZnO formation from aqueous solutions of zinc acetate and zinc nitrate. Chemistry of Materials, 26(14), 4119-4129. https://doi.org/10.1021/cm501561h

Lv, X., Zhang, L., Xing, F., & Lin, H. (2016). Controlled synthesis of monodispersed mesoporous silica nanoparticles: Particle size tuning and formation mechanism investigation. Microporous and Mesoporous Materials, 225, 238-244. https://doi.org/10.1016/j.micromeso.2016.02.036

Munusamy, P., Sanghavi, S., Varga, T., & Suntharampillai, T. (2014). Silica supported ceria nanoparticles: A hybrid nanostructure to increase stability and surface reactivity of nano-crystalline ceria. RSC Advances, 4(17), 8421-8430. https://doi.org/10.1039/C3RA46323B

Mura, S., Nicolas, J., & Couvreur, P. (2013). Stimuli-responsive nanocarriers for drug delivery. Nature Materials, 12(11), 991-1003. https://doi.org/10.1038/nmat3776

Nozawa, K., Gailhanou, H., Raison, L., Panizza, P., Ushiki, H., Sellier, E., Delville, J., & Delville, M. (2005). Smart control of monodisperse Stöber silica particles: Effect of reactant addition rate on growth process. Langmuir, 21(4), 1516-1523. https://doi.org/10.1021/la047361a

Othman, B., Greenwood, C., Abuelela, A., Bharath, A., Chen, S., Theodorou, I., Douglas, T., Uchida, M., Ryan, M., Merzaban, J., & Porter, A. (2016). Targeted cancer therapy: Correlative light-electron microscopy shows RGD-targeted ZnO nanoparticles dissolve in the intracellular environment of triple negative breast cancer cells and cause apoptosis with intratumor heterogeneity. Advanced Healthcare Materials, 5(11), 1248-1260. https://doi.org/10.1002/adhm.201500670

Park, J., & Oh, N. (2014). Endocytosis and exocytosis of nanoparticles in mammalian cells. International Journal of Nanomedicine, 9, 51-60. https://doi.org/10.2147/IJN.S39582

Rao, K. S., Srinivasa, R. K., Reddy, K. S., & Khan, M. S. (2005). A novel method for synthesis of silica nanoparticles. Journal of Colloid and Interface Science, 289(1), 125-131. https://doi.org/10.1016/j.jcis.2005.03.067

Silvestre-Albero, J., Sepúlveda-Escribano, A., & Reinoso, F. (2008). Preparation and characterization of zinc containing MCM-41 spheres. Microporous and Mesoporous Materials, 113(1-3), 362-369. https://doi.org/10.1016/j.micromeso.2008.01.006

Smittenaar, C., Petersen, K., Stewart, K., & Moitt, N. (2016). Cancer incidence and mortality projections in the UK until 2035. British Journal of Cancer, 115(9), 1147-1155. https://doi.org/10.1038/bjc.2016.295

Stöber, W., Fink, A., & Bohn, E. (1968). Controlled growth of monodisperse silica spheres in the micron size range. Journal of Colloid and Interface Science, 26(1), 62-69. https://doi.org/10.1016/0021-9797(68)90272-5

Suteewong, T., Sai, H., Lee, J., Bradbury, M., Hyeon, T., Gruner, S., & Wiesner, U. (2010). Ordered mesoporous silica nanoparticles with and without embedded iron oxide nanoparticles: Structure evolution during synthesis. Journal of Materials Chemistry, 20(36), 7807-7816. https://doi.org/10.1039/c0jm01342j

Tiwari, A., Wang, R., & Wei, B. (2016). Advanced surface engineering materials (1st ed., pp. 36-42). Beverly, MA: Scrivener Publishing.

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