Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

In vitro and Bioimaging Studies of Mesoporous Silica Nanocomposites Encapsulated Iron-oxide and Loaded Doxorubicin Drug (DOX/IO@Silica) as Magnetically Guided Drug Delivery System

Author(s): Hemant Kumar, Balaram Pani*, Jitender Kumar and Pramod Kumar*

Volume 24, Issue 10, 2023

Published on: 13 March, 2023

Page: [1297 - 1306] Pages: 10

DOI: 10.2174/1389201023666220428084920

Price: $65

Abstract

Background: In recent years, the delivery of drugs by nanocomposites has emerged as an exciting field of research for bio-imaging tools and targeted cancer treatment. The large surface area and porous volume of mesoporous silica nanocomposites (MSN’s) have gained a lot of interest for their application in the delivery of drugs and the magnetic properties of iron oxide (IO) nanocomposites play a key role in the targeted delivery system.

Methods: In this study, mesoporous silica encapsulated IO nanocomposites loaded with doxorubicin (DOX) were synthesized for the magnetically guided delivery of anticancer drugs. The synthesis of IO nanocomposites was done through the precipitation method, and then silica encapsulation and drug loading were done by the StÖber method.

Results: The magnetically driven delivery of the drug is produced by the encapsulation of magnetically active IO in the mesoporous silica shell. The controlled release of DOX is possible because of the MSN’s. TEM images show that the nanocomposites have a spherical morphology and average diameter in the range of 120 nm. Power-XRD data confirm the crystalline nature of nanocomposites. The strong absorption peak was observed in UV-Visible spectroscopy at 490 nm and quenching in fluorescence spectra confirms the encapsulation of DOX in the mesoporous silica shell. VSM data showed the magnetic nature of nanocomposites, with large magnetic susceptibility (74.88 emu/g). The use of DOX/IO@Silica nanocomposites as a sustainable drug release and targeted drug delivery vehicle has been reported here. The pH dependent release of DOX was studied and significant release was observed at lower pH. In-vitro cell viability assay and fluorescence imaging assay have demonstrated that these nanocomposites show significant dose-dependent toxicity to cancer cells in the presence of a magnetic field.

Conclusion: In-vitro studies via the MTT assay showed that these synthesized nanocomposites in culture are non-toxic to healthy cells compared to DOX-induced cytotoxicity due its controlled release and can be further strengthened by magnetic guidance. Therefore, due to its optical properties and potential for guided delivery of drug to the targeted site, these nanocomposites are ideal as an anticancer agent and bio-imaging prob.

Keywords: Mesoporous silica nanocomposites (MSN’s), core-shell iron oxide/silica nanocomposites (IO@Silica), the iron oxide (IO), magnetically guided drug delivery, (DOX), in-vivo.

« Previous Next »
Graphical Abstract

[1]
Yetisgin, A.A.; Cetinel, S.; Zuvin, M.; Kosar, A.; Kutlu, O. Therapeutic nanoparticles and their targeted delivery applications. Molecules, 2020, 25(9), 2193.
[http://dx.doi.org/10.3390/molecules25092193] [PMID: 32397080]
[2]
Agasti, S.S.; Rana, S.; Park, M.H.; Kim, C.K.; You, C.C.; Rotello, V.M. Nanoparticles for detection and diagnosis. Adv. Drug Deliv. Rev., 2010, 62(3), 316-328.
[http://dx.doi.org/10.1016/j.addr.2009.11.004] [PMID: 19913581]
[3]
Caruthers, S.D.; Wickline, S.A.; Lanza, G.M. Nanotechnological applications in medicine. Curr. Opin. Biotechnol., 2007, 18(1), 26-30.
[http://dx.doi.org/10.1016/j.copbio.2007.01.006] [PMID: 17254762]
[4]
Shi, J.; Votruba, A.R.; Farokhzad, O.C.; Langer, R. Nanotechnology in drug delivery and tissue engineering: From discovery to applica-tions. Nano Lett., 2010, 10(9), 3223-3230.
[http://dx.doi.org/10.1021/nl102184c] [PMID: 20726522]
[5]
Hyeon, T. Chemical synthesis of magnetic nanoparticles. Chem. Commun. (Camb.), 2003, 3(8), 927-934.
[http://dx.doi.org/10.1039/b207789b] [PMID: 12744306]
[6]
Jun, Y.W.; Choi, J.S.; Cheon, J. Heterostructured magnetic nanoparticles: Their versatility and high performance capabilities. Chem. Commun. (Camb.), 2007, (12), 1203-1214.
[http://dx.doi.org/10.1039/B614735F] [PMID: 17356759]
[7]
Estelrich, J.; Escribano, E.; Queralt, J.; Busquets, M.A. Iron oxide nanoparticles for magnetically-guided and magnetically-responsive drug delivery. Int. J. Mol. Sci., 2015, 16(4), 8070-8101.
[http://dx.doi.org/10.3390/ijms16048070] [PMID: 25867479]
[8]
Laurent, S.; Dutz, S.; Häfeli, U.O.; Mahmoudi, M. Magnetic fluid hyperthermia: Focus on superparamagnetic iron oxide nanoparticles. Adv. Colloid Interface Sci., 2011, 166(1-2), 8-23.
[http://dx.doi.org/10.1016/j.cis.2011.04.003] [PMID: 21601820]
[9]
Lee, N.; Hyeon, T. Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents. Chem. Soc. Rev., 2012, 41(7), 2575-2589.
[http://dx.doi.org/10.1039/C1CS15248C] [PMID: 22138852]
[10]
Prasad, P.N. Introduction to Nanomedicine and Nanobioengineering; John Wiley & Sons, 2012.
[11]
Ito, A.; Shinkai, M.; Honda, H.; Kobayashi, T. Medical application of functionalized magnetic nanoparticles. J. Biosci. Bioeng., 2005, 100(1), 1-11.
[http://dx.doi.org/10.1263/jbb.100.1] [PMID: 16233845]
[12]
Maeda, H.; Tsukigawa, K.; Fang, J. A retrospective 30 years after discovery of the enhanced permeability and retention effect of solid tumors: Next-generation chemotherapeutics and photodynamic therapy-problems, solutions, and prospects. Microcirculation, 2016, 23(3), 173-182.
[http://dx.doi.org/10.1111/micc.12228] [PMID: 26237291]
[13]
Li, K.; Nejadnik, H.; Daldrup-Link, H.E. Next-generation superparamagnetic iron oxide nanoparticles for cancer theranostics. Drug Discov. Today, 2017, 22(9), 1421-1429.
[http://dx.doi.org/10.1016/j.drudis.2017.04.008] [PMID: 28454771]
[14]
Tefft, B.J.; Uthamaraj, S.; Harburn, J.J.; Klabusay, M.; Dragomir-Daescu, D.; Sandhu, G.S. Cell labeling and targeting with superparamag-netic iron oxide nanoparticles. J. Vis. Exp., 2015, 2015(105)e53099
[http://dx.doi.org/10.3791/53099] [PMID: 26554870]
[15]
Brown, B.D.; Naldini, L. Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat. Rev. Genet., 2009, 10(8), 578-585.
[http://dx.doi.org/10.1038/nrg2628] [PMID: 19609263]
[16]
Wust, P.; Hildebrandt, B.; Sreenivasa, G.; Rau, B.; Gellermann, J.; Riess, H.; Felix, R.; Schlag, P.M. Hyperthermia in combined treatment of cancer. Lancet Oncol., 2002, 3(8), 487-497.
[http://dx.doi.org/10.1016/S1470-2045(02)00818-5] [PMID: 12147435]
[17]
Engelmann, U.; Buhl, E.M.; Baumann, M.; Schmitz-Rode, T.; Slabu, I. Agglomeration of magnetic nanoparticles and its effects on magnet-ic hyperthermia. Curr. Dir. Biomed. Eng., 2017, 3(2), 457-460.
[http://dx.doi.org/10.1515/cdbme-2017-0096]
[18]
Pankhurst, Q.A.; Connolly, J.; Jones, S.K.; Dobson, J. Applications of magnetic nanoparticles in biomedicine. J. Phys. D Appl. Phys., 2003, 36(13), R167.
[http://dx.doi.org/10.1088/0022-3727/36/13/201]
[19]
Chen, A.M.; Zhang, M.; Wei, D.; Stueber, D.; Taratula, O.; Minko, T.; He, H. Co-delivery of doxorubicin and Bcl-2 siRNA by mesoporous silica nanoparticles enhances the efficacy of chemotherapy in multidrug-resistant cancer cells. Small, 2009, 5(23), 2673-2677.
[http://dx.doi.org/10.1002/smll.200900621] [PMID: 19780069]
[20]
Kim, J.; Lee, J.E.; Lee, J.; Jang, Y.; Kim, S.W.; An, K.; Yu, J.H.; Hyeon, T. Generalized fabrication of multifunctional nanoparticle assem-blies on silica spheres. Angew. Chem. Int. Ed., 2006, 45(29), 4789-4793.
[http://dx.doi.org/10.1002/anie.200504107] [PMID: 16802396]
[21]
Roy, I.; Ohulchanskyy, T.Y.; Bharali, D.J.; Pudavar, H.E.; Mistretta, R.A.; Kaur, N.; Prasad, P.N. Optical tracking of organically modified silica nanoparticles as DNA carriers: A nonviral, nanomedicine approach for gene delivery. Proc. Natl. Acad. Sci. USA, 2005, 102(2), 279-284.
[http://dx.doi.org/10.1073/pnas.0408039101] [PMID: 15630089]
[22]
Ohulchanskyy, T.Y.; Roy, I.; Goswami, L.N.; Chen, Y.; Bergey, E.J.; Pandey, R.K.; Oseroff, A.R.; Prasad, P.N. Organically modified silica nanoparticles with covalently incorporated photosensitizer for photodynamic therapy of cancer. Nano Lett., 2007, 7(9), 2835-2842.
[http://dx.doi.org/10.1021/nl0714637] [PMID: 17718587]
[23]
Lu, C.W.; Hung, Y.; Hsiao, J.K.; Yao, M.; Chung, T.H.; Lin, Y.S.; Wu, S.H.; Hsu, S.C.; Liu, H.M.; Mou, C.Y.; Yang, C.S.; Huang, D.M.; Chen, Y.C. Bifunctional magnetic silica nanoparticles for highly efficient human stem cell labeling. Nano Lett., 2007, 7(1), 149-154.
[http://dx.doi.org/10.1021/nl0624263] [PMID: 17212455]
[24]
Xu, Z.P.; Zeng, Q.H.; Lu, G.Q.; Yu, A.B. Inorganic nanoparticles as carriers for efficient cellular delivery. Chem. Eng. Sci., 2006, 61(3), 1027-1040.
[http://dx.doi.org/10.1016/j.ces.2005.06.019]
[25]
Slowing, I.I.; Trewyn, B.G.; Lin, V.S.Y. Mesoporous silica nanoparticles for intracellular delivery of membrane-impermeable proteins. J. Am. Chem. Soc., 2007, 129(28), 8845-8849.
[http://dx.doi.org/10.1021/ja0719780] [PMID: 17589996]
[26]
Rosenholm, J.M.; Peuhu, E.; Bate-Eya, L.T.; Eriksson, J.E.; Sahlgren, C.; Lindén, M. Cancer-cell-specific induction of apoptosis using mesoporous silica nanoparticles as drug-delivery vectors. Small, 2010, 6(11), 1234-1241.
[http://dx.doi.org/10.1002/smll.200902355] [PMID: 20486218]
[27]
Sharma, R.K.; Das, S.; Maitra, A. Enzymes in the cavity of hollow silica nanoparticles. J. Colloid Interface Sci., 2005, 284(1), 358-361.
[http://dx.doi.org/10.1016/j.jcis.2004.10.006] [PMID: 15752825]
[28]
Van Speybroeck, M.; Mellaerts, R.; Mols, R.; Thi, T.D.; Martens, J.A.; Van Humbeeck, J.; Annaert, P.; Van den Mooter, G.; Augustijns, P. Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica. Eur. J. Pharm. Sci., 2010, 41(5), 623-630.
[http://dx.doi.org/10.1016/j.ejps.2010.09.002] [PMID: 20850527]
[29]
Maleki, A.; Kettiger, H.; Schoubben, A.; Rosenholm, J.M.; Ambrogi, V.; Hamidi, M. Mesoporous silica materials: From physico-chemical properties to enhanced dissolution of poorly water-soluble drugs. J. Control. Release, 2017, 262, 329-347.
[http://dx.doi.org/10.1016/j.jconrel.2017.07.047] [PMID: 28778479]
[30]
Wang, Y.; Zhao, Q.; Han, N.; Bai, L.; Li, J.; Liu, J.; Che, E.; Hu, L.; Zhang, Q.; Jiang, T.; Wang, S. Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomedicine, 2015, 11(2), 313-327.
[http://dx.doi.org/10.1016/j.nano.2014.09.014] [PMID: 25461284]
[31]
Argyo, C.; Weiss, V.; Bräuchle, C.; Bein, T. Multifunctional mesoporous silica nanoparticles as a universal platform for drug delivery. Chem. Mater., 2014, 26(1), 435-451.
[http://dx.doi.org/10.1021/cm402592t]
[32]
Stöber, W.; Fink, A.; Bohn, E. Controlled growth of monodisperse silica spheres in the micron size range. J. Colloid Interface Sci., 1968, 26(1), 62-69.
[http://dx.doi.org/10.1016/0021-9797(68)90272-5]
[33]
Santra, S.; Kaittanis, C.; Grimm, J.; Perez, J.M. Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging. Small, 2009, 5(16), 1862-1868.
[http://dx.doi.org/10.1002/smll.200900389] [PMID: 19384879]
[34]
Sahoo, B.; Devi, K.S.P.; Sahu, S.K.; Nayak, S.; Maiti, T.K.; Dhara, D.; Pramanik, P. Facile preparation of multifunctional hollow silica nanoparticles and their cancer specific targeting effect. Biomater. Sci., 2013, 1(6), 647-657.
[http://dx.doi.org/10.1039/c3bm00007a] [PMID: 32481837]
[35]
Tadanaga, K.; Morita, K.; Mori, K.; Tatsumisago, M. Synthesis of monodispersed silica nanoparticles with high concentration by the Stöber process. J. Sol-Gel Sci. Technol., 2013, 68(2), 341-345.
[http://dx.doi.org/10.1007/s10971-013-3175-6]
[36]
Tang, F.; Li, L.; Chen, D. Mesoporous silica nanoparticles: Synthesis, biocompatibility and drug delivery. Adv. Mater., 2012, 24(12), 1504-1534.
[http://dx.doi.org/10.1002/adma.201104763] [PMID: 22378538]
[37]
Chen, J.F.; Ding, H.M.; Wang, J.X.; Shao, L. Preparation and characterization of porous hollow silica nanoparticles for drug delivery appli-cation. Biomaterials, 2004, 25(4), 723-727.
[http://dx.doi.org/10.1016/S0142-9612(03)00566-0] [PMID: 14607511]
[38]
Thommes, M.; Kaneko, K.; Neimark, A.V.; Olivier, J.P.; Rodriguez-Reinoso, F.; Rouquerol, J.; Sing, K.S.W. Physisorption of gases, with special reference to the evaluation of surface area and pore size distribution (IUPAC Technical Report). Pure Appl. Chem., 2015, 87(9-10), 1051-1069.
[http://dx.doi.org/10.1515/pac-2014-1117]
[39]
Kumar, P.; Agnihotri, S. Synthesis of DOX drug conjugation and citric acid stabilized superparamagnetic iron-oxide nanoparticles for drug delivery. Biochem. Physiol. Open Access, 2016, 1(05), 1.
[http://dx.doi.org/10.4172/2168-9652.1000194]
[40]
Xu, Z.; Hou, Y.; Sun, S. Magnetic core/shell Fe3O4/Au and Fe3O4/Au/Ag nanoparticles with tunable plasmonic properties. J. Am. Chem. Soc., 2007, 129(28), 8698-8699.
[http://dx.doi.org/10.1021/ja073057v] [PMID: 17590000]
[41]
Kato, Y.; Ozawa, S.; Miyamoto, C.; Maehata, Y.; Suzuki, A.; Maeda, T.; Baba, Y. Acidic extracellular microenvironment and cancer. Cancer Cell Int., 2013, 13(1), 89.
[http://dx.doi.org/10.1186/1475-2867-13-89] [PMID: 24004445]
[42]
Das, S.; Jain, T.K.; Maitra, A. Inorganic-organic hybrid nanoparticles from n-octyl triethoxy silane. J. Colloid Interface Sci., 2002, 252(1), 82-88.
[http://dx.doi.org/10.1006/jcis.2002.8404] [PMID: 16290765]
[43]
Kumar, H.; Agnihotri, S.; Roy, I.; Pani, B.; Kumar, P. Microemulsion mediated multifunction of doxorubicin encapsulated: Ingenta con-nect. Adv. Sci. Eng. Med., 2020, 12(9), 1166-1173.

Rights & Permissions Print Cite
Article Metrics
27
2
© 2024 Bentham Science Publishers | Privacy Policy