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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Increased Toxicity of Doxorubicin Encapsulated into pH-Responsive Poly(β-Amino Ester)-Functionalized MCM-41 Silica Nanoparticles

Author(s): Alejandro Ávila-Ortega, Leydi Maribel Carrillo-Cocom*, Christofer Enmanuel Olán-Noverola, Geovanny I. Nic-Can, Alfredo Rafael Vilchis-Nestor and William Alejandro Talavera-Pech

Volume 17, Issue 9, 2020

Page: [799 - 805] Pages: 7

DOI: 10.2174/1567201817999200728123915

Price: $65

Abstract

Background: The encapsulation of anti-cancer drugs in stimulus-sensitive release systems may provide advantages such as enhanced drug toxicity in tumour tissue cells due to increased intracellular drug release. Encapsulation may also improve release in targeted tissue due to the response to a stimulus such as pH, which is lower in the tumour tissue microenvironment. Here, we evaluated the in vitro toxicity of the Drug Doxorubicin (DOX) loaded into a release system based on poly(β-amino ester)- modified MCM-41 silica nanoparticles.

Methods: The MCM-41-DOX-PbAE release system was obtained by loading DOX into MCM-41 nanoparticles amino-functionalized with 3-aminopropyltriethoxysilane (APTES) and then coated with a pH-responsive poly(β-amino ester) (PbAE). The physicochemical characteristics of the release system were evaluated through TEM, FTIR and TGA. Cytotoxicity assays were performed on the MCM-41- DOX-PbAE system to determine their effects on the inhibition of human MCF-7 breast cancer cell proliferation after 48 h of exposure through crystal violet assay; the investigated systems included MCF-7 cells with MCM-41, PbAE, and MCM-41-PbAE alone. Additionally, the release of DOX and the change in pH in vitro were determined.

Results: The physicochemical characteristics of the synthesized MCM-41-PbAE system were confirmed, including the nanoparticle size, spherical morphology, mesoporous ordered structure, and presence of PbAE on the surface of the MCM-41 nanoparticles. Likewise, we demonstrated that the release of DOX from the MCM-41-DOX-PbAE system promoted an important reduction in MCF-7 cell viability (~ 70%) compared to the values obtained with MCM-41, PbAE, and MCM-41-PbAE, as well as a reduction in the viability under treatment with just DOX (~ 50%).

Conclusion: The results suggest that all the components of the release system are biocompatible and that the encapsulation of DOX in MCM-41-PbAE could allow better intracellular release, which would probably increase the availability and toxic effect of DOX.

Keywords: Cancer cells, cytotoxicity, doxorubicin, drug delivery, mesoporous silica nanoparticles, pH-sensitive.

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[1]
Narvekar, M.; Xue, H.Y.; Eoh, J.Y.; Wong, H.L. Nanocarrier for poorly water-soluble anticancer drugs--barriers of translation and solutions. AAPS PharmSciTech, 2014, 15(4), 822-833.
[http://dx.doi.org/10.1208/s12249-014-0107-x ] [PMID: 24687241]
[2]
Cherif, H.; Bacha, S.; Habibech, S.; Cheikhrouhou, S.; Chaouech, N.; Chabbou, A.; Megdiche, M. Chemotherapy toxicity in advanced non-small cell lung cancer and its impact on survival. Eur. Respir. J., 2016, 48, PA4841.
[3]
Doroshow, J.H. Doxorubicin-induced cardiac toxicity. N. Engl. J. Med., 1991, 324(12), 843-845.
[http://dx.doi.org/10.1056/NEJM199103213241210 ] [PMID: 1997858]
[4]
Pugazhendhi, A.; Edison, T.N.J.I.; Velmurugan, B.K.; Jacob, J.A.; Karuppusamy, I. Toxicity of Doxorubicin (Dox) to different experimental organ systems. Life Sci., 2018, 200, 26-30.
[http://dx.doi.org/10.1016/j.lfs.2018.03.023 ] [PMID: 29534993]
[5]
Qiao, Y.; Wan, J.; Zhou, L.; Ma, W.; Yang, Y.; Luo, W.; Yu, Z.; Wang, H. Stimuli-responsive nanotherapeutics for precision drug delivery and cancer therapy. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2019, 11(1), e1527.
[http://dx.doi.org/10.1002/wnan.1527 ] [PMID: 29726115]
[6]
Ngoune, R.; Peters, A.; von Elverfeldt, D.; Winkler, K.; Pütz, G. Accumulating nanoparticles by EPR: a route of no return. J. Control. Release, 2016, 238, 58-70.
[http://dx.doi.org/10.1016/j.jconrel.2016.07.028 ] [PMID: 27448444]
[7]
Brannon-Peppas, L.; Blanchette, J.O. Nanoparticle and targeted systems for cancer therapy. Adv. Drug Deliv. Rev., 2004, 56(11), 1649-1659.
[http://dx.doi.org/10.1016/j.addr.2004.02.014 ] [PMID: 15350294]
[8]
Bao, B.Q.; Le, N.H.; Nguyen, D.H.T.; Tran, T.V.; Pham, L.P.T.; Bach, L.G.; Ho, H.M.; Nguyen, T.H.; Nguyen, D.H. Evolution and present scenario of multifunctionalized mesoporous nanosilica platform: a mini review. Mater. Sci. Eng. C, 2018, 91, 912-928.
[http://dx.doi.org/10.1016/j.msec.2018.07.008 ] [PMID: 30033325]
[9]
Wen, J.; Yang, K.; Liu, F.; Li, H.; Xu, Y.; Sun, S. Diverse gatekeepers for mesoporous silica nanoparticle based drug delivery systems. Chem. Soc. Rev., 2017, 46(19), 6024-6045.
[http://dx.doi.org/10.1039/C7CS00219J ] [PMID: 28848978]
[10]
Peer, D.; Karp, J.M.; Hong, S.; Farokhzad, O.C.; Margalit, R.; Langer, R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol., 2007, 2(12), 751-760.
[http://dx.doi.org/10.1038/nnano.2007.387 ] [PMID: 18654426]
[11]
Farokhzad, O.C.; Langer, R. Impact of nanotechnology on drug delivery. ACS Nano, 2009, 3(1), 16-20.
[http://dx.doi.org/10.1021/nn900002m ] [PMID: 19206243]
[12]
Anselmo, A.C.; Mitragotri, S. A review of clinical translation of inorganic nanoparticles. AAPS J., 2015, 17(5), 1041-1054.
[http://dx.doi.org/10.1208/s12248-015-9780-2 ] [PMID: 25956384]
[13]
Rosenholm, J.M.; Meinander, A.; Peuhu, E.; Niemi, R.; Eriksson, J.E.; Sahlgren, C.; Lindén, M. Targeting of porous hybrid silica nanoparticles to cancer cells. ACS Nano, 2009, 3(1), 197-206.
[http://dx.doi.org/10.1021/nn800781r ] [PMID: 19206267]
[14]
Wagner, E.; Ogris, M.; Zauner, W. Polylysine-based transfection systems utilizing receptor-mediated delivery. Adv. Drug Deliv. Rev., 1998, 30(1-3), 97-113.
[http://dx.doi.org/10.1016/S0169-409X(97)00110-5 ] [PMID: 10837605]
[15]
Choksakulnimitr, S.; Masuda, S.; Tokuda, H.; Takakura, Y.; Hashida, M. In vitro cytotoxicity of macromolecules in different cell culture systems. J. Control. Release, 1995, 34(3), 233-241.
[http://dx.doi.org/10.1016/0168-3659(95)00007-U]
[16]
Fischer, D.; Bieber, T.; Li, Y.; Elsässer, H.P.; Kissel, T. A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity. Pharm. Res., 1999, 16(8), 1273-1279.
[http://dx.doi.org/10.1023/A:1014861900478 ] [PMID: 10468031]
[17]
Putnam, D.; Gentry, C.A.; Pack, D.W.; Langer, R. Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini. Proc. Natl. Acad. Sci. USA, 2001, 98(3), 1200-1205.
[http://dx.doi.org/10.1073/pnas.98.3.1200 ] [PMID: 11158617]
[18]
Tang, S.; Yin, Q.; Zhang, Z.; Gu, W.; Chen, L.; Yu, H.; Huang, Y.; Chen, X.; Xu, M.; Li, Y. Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer. Biomaterials, 2014, 35(23), 6047-6059.
[http://dx.doi.org/10.1016/j.biomaterials.2014.04.025 ] [PMID: 24797883]
[19]
Shen, Y.; Tang, H.; Zhan, Y.; Van Kirk, E.A.; Murdoch, W.J. Degradable poly(beta-amino ester) nanoparticles for cancer cytoplasmic drug delivery. Nanomedicine (Lond.), 2009, 5(2), 192-201.
[http://dx.doi.org/10.1016/j.nano.2008.09.003 ] [PMID: 19223244]
[20]
Fernando, I.R.; Ferris, D.P.; Frasconi, M.; Malin, D.; Strekalova, E.; Yilmaz, M.D.; Ambrogio, M.W.; Algaradah, M.M.; Hong, M.P.; Chen, X.; Nassar, M.S.; Botros, Y.Y.; Cryns, V.L.; Stoddart, J.F. Esterase- and pH-responsive poly(β-amino ester)-capped mesoporous silica nanoparticles for drug delivery. Nanoscale, 2015, 7(16), 7178-7183.
[http://dx.doi.org/10.1039/C4NR07443B ] [PMID: 25820516]
[21]
Zhou, M.; Zhang, X.; Xie, J.; Qi, R.; Lu, H.; Leporatti, S.; Chen, J.; Hu, Y. pH-sensitive poly(β-amino ester)s nanocarriers facilitate the inhibition of drug resistance in breast cancer cells. Nanomaterials (Basel), 2018, 8(11), 952.
[http://dx.doi.org/10.3390/nano8110952 ] [PMID: 30463238]
[22]
Talavera, P.; Esparza-Ruiz, A.; Quintana-Owen, P.; Vilchis-Nestor, A.; Bárron-Zambrano, J.; Ávila-Ortega, A. Synthesis of pH-sensitive poly(β-amino ester)-coated mesoporous silica nanoparticles for the controlled release of drugs. Appl. Nanosci., 2018, 8, 853-866.
[http://dx.doi.org/10.1007/s13204-018-0716-x]
[23]
Chang, B.; Sha, X.; Guo, J.; Jiao, Y.; Wang, G.; Yang, W. Thermo and pH dual responsive, polymer shell coated, magnetic mesoporous silica nanoparticles for controlled drug release. J. Mater. Chem., 2011, 21(5), 9239-9274.
[http://dx.doi.org/10.1039/c1jm10631g]
[24]
Tang, H.; Guo, J.; Sun, Y.; Chang, B.; Ren, Q.; Yang, W. Facile synthesis of pH sensitive polymer-coated mesoporous silica nanoparticles and their application in drug delivery. Int. J. Pharm., 2011, 421(2), 388-396.
[http://dx.doi.org/10.1016/j.ijpharm.2011.10.013 ] [PMID: 22001840]
[25]
Feoktistova, M.; Geserick, P.; Leverkus, M. Crystal violet assay for determining viability of cultured cells. Cold Spring Harb. Protoc., 2016, 2016, 4.
[http://dx.doi.org/10.1101/pdb.prot087379]
[26]
Chung, P.; Kumar, R.; Pruski, M.; Lin, V.S. Temperature responsive solution partition of organic-inorganic hybrid poly(n‐isopropylacrylamide)‐coated mesoporous silica nanospheres. Adv. Funct. Mater., 2008, 18(9), 1390-1398.
[http://dx.doi.org/10.1002/adfm.200701116]
[27]
Radu, D.R.; Lai, C.Y.; Wiench, J.W.; Pruski, M.; Lin, V.S. Gatekeeping layer effect: a poly(lactic acid)-coated mesoporous silica nanosphere-based fluorescence probe for detection of amino-containing neurotransmitters. J. Am. Chem. Soc., 2004, 126(6), 1640-1641.
[http://dx.doi.org/10.1021/ja038222v ] [PMID: 14871088]
[28]
Zhu, Y.; Shi, J. Mesoporous core-shell structure for pH-controlled storage and release of water-soluble drug. Microporous Mesoporous Mater., 2007, 103(1-3), 243-249.
[http://dx.doi.org/10.1016/j.micromeso.2007.02.012]
[29]
Holmes, S.; Zholobenko, V.; Thursfield, A.; Plaisted, R.; Cundy, C.; Dwyer, J. In situ FTIR study of the formation of MCM-41. J. Chem. Soc., Faraday Trans., 1998, 94, 2025-2032.
[http://dx.doi.org/10.1039/a801898g]
[30]
Stuart, B.H. Infrared spectroscopy: fundamentals and applications; Wiley, 2004.
[http://dx.doi.org/10.1002/0470011149]
[31]
Martino, L.; Scandola, M.; Jiang, Z. Enzymatic synthesis, thermal and crystalline properties of a poly(β-amino ester) and poly(lactone-co-β-amino ester) copolymers. Polymer (Guildf.), 2012, 53(9), 1839-1848.
[http://dx.doi.org/10.1016/j.polymer.2012.03.005]
[32]
Gangwal, J.; Kulkarni, M. Synthesis and characterization of bile acid-based poly β amino esters for paclitaxel delivery. J. Appl. Polym. Sci., 2011, 122(1), 220-232.
[http://dx.doi.org/10.1002/app.34144]
[33]
Lebret, V.; Raehm, L.; Durand, J.; Smaïhi, M.; Werts, M.; Desce, M.; Méthy-Gonnod, D.; Dubernet, C. Surface functionalization of two-photon dye-doped mesoporous silica nanoparticles with folic acid: cytotoxicity studies with HeLa and MCF-7 cancer cells. J. Sol-Gel Sci. Technol., 2008, 48, 32-39.
[http://dx.doi.org/10.1007/s10971-008-1724-1]
[34]
Vivero-Escoto, J.L.; Slowing, I.I.; Trewyn, B.G.; Lin, V.S. Mesoporous silica nanoparticles for intracellular controlled drug delivery. Small, 2010, 6(18), 1952-1967.
[http://dx.doi.org/10.1002/smll.200901789 ] [PMID: 20690133]
[35]
He, Q.; Shi, J.; Chen, F.; Zhu, M.; Zhang, L. An anticancer drug delivery system based on surfactant-templated mesoporous silica nanoparticles. Biomaterials, 2010, 31(12), 3335-3346.
[http://dx.doi.org/10.1016/j.biomaterials.2010.01.015 ] [PMID: 20106517]
[36]
Sankaranarayanan, J.; Mahmoud, E.A.; Kim, G.; Morachis, J.M.; Almutairi, A. Multiresponse strategies to modulate burst degradation and release from nanoparticles. ACS Nano, 2010, 4(10), 5930-5936.
[http://dx.doi.org/10.1021/nn100968e ] [PMID: 20828178]
[37]
Tang, S.; Yin, Q.; Su, J.; Sun, H.; Meng, Q.; Chen, Y.; Chen, L.; Huang, Y.; Gu, W.; Xu, M.; Yu, H.; Zhang, Z.; Li, Y. Inhibition of metastasis and growth of breast cancer by pH-sensitive poly (β-amino ester) nanoparticles co-delivering two siRNA and paclitaxel. Biomaterials, 2015, 48, 1-15.
[http://dx.doi.org/10.1016/j.biomaterials.2015.01.049 ] [PMID: 25701027]
[38]
Narkhede, N.; Uttam, B.; Kandi, R.; Rao, C.P. Silica-calix hybrid composite of allyl calix[4]arene covalently linked to MCM-41 nanoparticles for sustained release of doxorubicin into cancer cells. ACS Omega, 2018, 3(1), 229-239.
[http://dx.doi.org/10.1021/acsomega.7b01852 ] [PMID: 30023773]
[39]
Zhu, H.; Sarkar, S.; Scott, L.; Danelisen, I.; Trush, M.A.; Jia, Z.; Li, Y.R. Doxorubicin redox biology: redox cycling, topoisomerase inhibition, and oxidative stress. React. Oxyg. Species (Apex), 2016, 1(3), 189-198.
[http://dx.doi.org/10.20455/ros.2016.835 ] [PMID: 29707645]

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