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On the cytotoxicity of a cationic tertiary amine PEGylated nanogel as nanocarrier for anticancer therapies

Published online by Cambridge University Press:  07 June 2018

Lizbeth A. Manzanares-Guevara
Affiliation:
Centro de Graduados e Investigación en Química, Instituto Tecnológico de Tijuana, Tijuana, Baja California, C.P. 22000, México
Angel Licea-Claverie*
Affiliation:
Centro de Graduados e Investigación en Química, Instituto Tecnológico de Tijuana, Tijuana, Baja California, C.P. 22000, México
Irasema Oroz-Parra
Affiliation:
Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Ensenada, Baja California, México Facultad de Ciencias Marinas, Universidad Autónoma de Baja California, Ensenada, Baja California, C.P. 22860, México
Alexei F. Licea-Navarro
Affiliation:
Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Ensenada, Baja California, México
*
Address all correspondence to Prof. Dr. Angel Licea-Claverie at aliceac@tectijuana.mx
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Abstract

Cationic PEGylated nanogels based on poly(N,N-diethylaminoethyl methacrylate) (PDEAEM) were prepared varying the ratio of PDEAEM to polyethyleneglycol (PEG), the initiator, and the crosslinker; resulting in nanogels of different surface charge (zeta-potential) and hydrodynamic diameter. Nanogels without PEG (100% PDEAEM) and nanogels containing 45 wt.% of PDEAEM were cytotoxic to human colon cancer cell line (HCT-116). Nanogels containing 20 wt.% or less of PDEAEM provided with a PEG shell were non-cytotoxic even at a concentration of 1 mg/mL. These nanogels loaded with 5-fluorouracil turned to be cytotoxic provoking cell death by apoptosis. Nanogels were also studied loaded with gold nanoparticles.

Type
Research Letters
Copyright
Copyright © Materials Research Society 2018 

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References

1.Shen, M., Huang, Y., Han, L., Qin, J., Fang, X., Wang, J., and Yang, V.C.: Multifunctional drug delivery system for targeting tumor and its acidic microenvironment. J. Control. Release 161, 884 (2012).Google Scholar
2.Brannon-Peppas, L. and Blanchette, J.O.: Nanoparticle and targeted systems for cancer therapy. Adv. Drug Deliv. Rev. 64, 206 (2012).Google Scholar
3.Sun, L., Wu, Q., Peng, F., Liu, L., and Gong, C.: Strategies of polymeric nanoparticles for enhanced internalization in cancer therapy. Collloid Surf. B. 135, 56 (2015).Google Scholar
4.Delcea, M., Möhwald, H., and Skirtach, A.G.: Stimuli-responsive LbL capsules and nanoshells for drug delivery. Adv. Drug Deliv. Rev. 63, 730 (2011).Google Scholar
5.Chan, A., Orme, R.P., Fricker, R.A., and Roach, P.: Remote and local control of stimuli responsive materials for therapeutic applications. Adv. Drug Deliv. Rev. 65, 497 (2012).Google Scholar
6.Tapeinos, C., Efthimiadou, E.K., Boukos, N., Charitidis, C.A., Koklioti, M., and Kordas, G.: Microspheres as therapeutic delivery agents: synthesis and biological evaluation of pH responsiveness. J. Mater. Chem. B. 1, 194 (2013).Google Scholar
7.Tapeinos, C., Efthimiadou, E.K., Boukos, N., and Kordas, G.: Sustained release profile of quatro stimuli nanocontainers as a multisensitive vehicle exploiting cancer characteristics. Colloid Surf. B. 148, 95 (2016).Google Scholar
8.Karimi, M., Zangabad, P.S., Ghasemi, A., Amiri, M., Bahrami, M., Malekzad, H., Asl, H.G., Mahdieh, Z., Bozorgomid, M., Ghasemi, A., Boyuk, M.R.R.T., and Hamblin, M.R.: Temperature-responsive smart nanocarriers for delivery of therapeutic agents: applications and recent advances. ACS Appl. Mater. Interfaces 8, 21107 (2016).Google Scholar
9.Ramasamy, T., Ruttala, H.B., Gupta, B., Poudel, B.K., Choi, H.-G., Yong, C.S., and Kim, J.O.: Smart chemistry-based nanosized drug delivery systems for systemic applications: a comprehensive review. J. Control. Release 258, 226 (2017).Google Scholar
10.Kowalczuk, A., Trzcinska, R., Trzebicka, B., Müller, A.H.E., Dworak, A., and Tsvetanov, C.B.: Loading of polymer nanocarriers: factors, mechanisms and applications. Prog. Polym. Sci. 39, 43 (2014).Google Scholar
11.Mura, S., Nicolas, J., and Couvreur, P.: Stimuli-responsive nanocarriers for drug delivery. Nat. Mater. 12, 991 (2013).Google Scholar
12.Cheng, R., Meng, F., Deng, C., Klok, H.-A., and Zhong, Z.: Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery. Biomaterials. 34, 3647 (2013).Google Scholar
13.Tamura, M., Ichinohe, S., Tamura, A., Ikeda, Y., and Nagasaki, Y.: In vitro and in vivo characteristics of core–shell type nanogel particles: optimization of core cross-linking density and surface poly(ethylene glycol) density in PEGylated nanogels. Acta Biomat. 7, 3354 (2011).Google Scholar
14.Ikeda, Y. and Nagasaki, Y.: PEGylation technology in nanomedicine. Adv. Polym. Sci. 247, 115 (2012).Google Scholar
15.Hwang, T.-L., Aljuffali, I.A., Lin, C.-F., Chang, Y.-T., and Fang, J.-Y.: Cationic additives in nanosystems activate cytotoxicity and inflammatory response of human neutrophils: lipid nanoparticles versus polymeric nanoparticles. Int. J. Nanomed. 10, 371 (2015).Google Scholar
16.Van de Wetering, P., Moret, E.E., Schuurmans-Nieuwenbroek, N.M., van Steenbergen, M.J., and Hennink, W.E.: Structure–activity relationships of water-soluble cationic methacrylate/methacrylamide polymers for nonviral gene delivery. Bioconjug. Chem. 10, 589 (1999).Google Scholar
17.Xu, P., Van Kirk, E.A., Murdoch, W.J., Zhan, Y., Isaak, D.D., Radosz, M., and Shen, Y.: Anticancer efficacies of Cisplatin-releasing pH-responsive nanoparticles. Biomacromolecules 7, 829 (2006).Google Scholar
18.Arvizo, R.R., Miranda, O.R., Thompson, M.A., Pabelick, C.M., Bhattacharya, R., Robertson, J.D., Rotello, V.M., Prakash, Y.S., and Mukherjee, P.: Effect of nanoparticle surface charge at the plasma membrane and beyond. Nano Lett. 10, 2543 (2010).Google Scholar
19.Van Cutsem, E., Peeters, M., Verslype, C., Filez, L., Haustermans, K., and Janssens, J.: The medical treatment of colorectal cancer: actual status and new developments. Hepatogastroenterology 46, 709 (1999).Google Scholar
20.Amalvy, J.I., Wanless, E.J., Li, Y., Michailidou, V., and Armes, S.P.: Synthesis and characterization of novel pH-responsive microgels based on tertiary amine methacrylates. Langmuir 20, 8992 (2004).Google Scholar
21.Pikabea, A., Ramos, J., and Forcada, J.: Production of cationic nanogels with potential use in controlled drug delivery. Part. Part. Syst. Charact. 31, 101 (2014).Google Scholar
22.Marek, S.R., Conn, C.A., and Peppas, N.A.: Cationic nanogels based on diethylaminoethyl methacrylate. Polymer 51, 1237 (2010).Google Scholar
23.Oishi, M., Hayashi, H., Iijima, M., and Nagasaki, Y.: Endosomal release and intracellular delivery of anticancer drugs using pH-sensitive PEGylated nanogels. J. Mater. Chem. 17, 3720 (2007).Google Scholar
24.Aguirre, G., Villar-Alvarez, E., Gonzalez, A., Ramos, J., Taboada, P., and Forcada, J.: Biocompatible stimuli-responsive nanogels for controlled antitumor drug delivery. J. Polym. Sci. A: Polym. Chem. 54, 1694 (2016).Google Scholar
25.Kaihara, S., Matsumura, S., and Fisher, J.P.: Synthesis and properties of Poly[poly(ethylene glycol)-co-cyclic acetal] based hydrogels. Macromol. 40, 7625 (2007).Google Scholar
26.Serrano-Medina, A., Oroz-Parra, I., Gomez-Resendiz, V.E., Licea-Navarro, A., Licea-Claverie, A., and Cornejo-Bravo, J.M.: Temperature and pH sensitive core-shell nanogels as efficient carriers of doxorubicin with potential application in lung cancer treatment. Int. J. Polym. Mater. Polym. Biomat. 67, 20 (2018).Google Scholar
27.Manzanares-Guevara, L.A., Licea-Claverie, A., and Paraguay-Delgado, F.: Preparation of stimuli responsive nanogels based on poly(N,N-diethylaminoethyl methacrylate) by a simple “surfactant-free” methodology. Soft. Mater. 16, 37 (2018).Google Scholar
28.Torchilin, V.P.: Structure and design of polymeric surfactant-based drug delivery systems. J. Control. Release 73, 137 (2001).Google Scholar
29.Mohamed, M.B., Adbel-Ghani, N.T., El-Borady, O.M., and El-Sayed, M.A.: 5-Fluorouracil induces plasmonic coupling in gold nanospheres: new generation of chemotherapeutic agents. J. Nanomed. Nanotechol. 3, 146 (2012).Google Scholar
30.Suzuki, H. and Bae, Y.H.: Evaluation of drug penetration with cationic micelles and their penetration mechanism using an in vitro tumor model. Biomaterials 98, 120 (2016).Google Scholar
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