Polyinosinic:polycytidylic acid loading onto different generations of PAMAM dendrimer-coated magnetic nanoparticles
Poly (I:C), which is a synthetic double-stranded RNA, have significant toxicity on tumor cells. The immobilization of Poly (I:C) onto nanoparticles is important for the fabrication of targeted delivery systems. In this study, different generations of newly synthesized PAMAM dendron-coated magnetic nanoparticles (DcMNP) which can be targeted to the tumor site under magnetic field were efficiently loaded for the first time with Poly (I:C). Different generations of DcMNPs (G2, G3, G4, G5, G6, and G7) were synthesized. Poly (I:C) activation was achieved in the presence of EDC and 1-methylimidazole. Loading of Poly (I:C) onto DcMNPs was followed by agarose gel electrophoresis. Acidic reaction conditions were found as superior to basic and neutral for binding of Poly (I:C). In addition, having more functional groups at the surface, higher generations (G7, G6, and G5) of PAMAM DcMNPs were found more suitable as a delivery system for Poly (I:C). Further in vitro and in vivo analyses of Poly (I:C)/PAMAM magnetic nanoparticles may provide new opportunities for the selective targeting and killing of tumor cells.
KeywordsPoly (I:C) Magnetic nanoparticles Targeted delivery system Cancer therapy
This study was supported by TÜBİTAK (TBAG-109T949 and TBAG-2215), and Middle East Technical University (BAP-07-02-2010-06).
Conflict of interest
The authors declare that they have no conflict of interest.
- Butowski N, Lamborn KR, Lee BL, Prados MD, Cloughesy T, DeAngelis LM, Abrey L, Fink K, Lieberman F, Mehta M, Ian Robins H, Junck L, Salazar AM, Chang SM (2009) A North American brain tumor consortium phase II study of poly-ICLC for adult patients with recurrent anaplastic gliomas. J Neurooncol 91:183–189CrossRefGoogle Scholar
- Chen L, Ding Y, Wang Y, Liu X, Babu R, Ravis W, Yan W (2013) Codelivery of zoledronic acid and doublestranded RNA from core–shell nanoparticles. Int J Nanomed 8:137–145Google Scholar
- Du X, Poltorak A, Wei Y, Beutler B (2000) Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw 11:362–371Google Scholar
- Gomori G (1948, December) Histochemical demonstration of sites of phosphamidase activity. In Proceedings of the society for experimental biology and medicine, Vol. 69, No. 3. Society for Experimental Biology and Medicine, Royal Society of Medicine, New York, p 407–409Google Scholar
- Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ, Yamaguchi O, Otsu K, Tsujimura T, Koh CS, Reis e Sousa C, Matsuura Y, Fujita T, Akira S (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101–105CrossRefGoogle Scholar
- Ludeman SM (1999) The chemistry of the metabolites of cyclophosphamide. Curr Pharm Des 5:627–644Google Scholar
- Matsumoto M, Funami K, Oshiumi H, Seya T (2004) Toll-like receptor 3: a link between toll-like receptor, interferon and viruses. Microbiol Immunol 48:147–154Google Scholar
- Meyer J, Weinmann JP (1957) Occurrence of phosphamidase activity in keratinizing epithelia1. J Investig Dermatol 29:393–405Google Scholar
- Salem ML, El-Naggar SA, Kadima A, Gillanders WE, Cole DJ (2006) The adjuvant effects of the toll-like receptor 3 ligand polyinosinic-cytidylic acid poly (I:C) on antigen-specific CD8 + T cell responses are partially dependent on NK cells with the induction of a beneficial cytokine milieu. Vaccine 24:5119–5132CrossRefGoogle Scholar
- Shukoor MI, Natalio F, Metz N, Glube N, Tahir MN, Therese HA, Ksenofontov V, Theato P, Langguth P, Boissel JP, Schröder HC, Müller WE, Tremel W (2008) dsRNA-functionalized multifunctional gamma-Fe2O3 nanocrystals: a tool for targeting cell surface receptors. Angew Chem Int Ed Engl 47:4748–4752CrossRefGoogle Scholar
- Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, Mudd S, Shamel L, Sovath S, Goode J, Alexopoulou L, Flavell RA, Beutler B (2004) Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci USA 101:3516–3521CrossRefGoogle Scholar
- Weber A, Kirejczyk Z, Besch R, Potthoff S, Leverkus M, Häcker G (2010) Proapoptotic signalling through Toll-like receptor-3 involves TRIF-dependent activation of caspase-8 and is under the control of inhibitor of apoptosis proteins in melanoma cells. Cell Death Differ 17:942–951CrossRefGoogle Scholar