1. New folic acid-functionalized acrylate nanoparticles for an active targeting of DNA towards cancer cells
- Author
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Bellotti Elena, Cristallini Caterina, Paonessa Siriana, Barbani Niccoletta, and Cascone Maria Grazia
- Subjects
Acrylate ,Histology ,nanoparticle ,technology, industry, and agriculture ,biomaterial ,Biomedical Engineering ,Nanoparticle ,Bioengineering ,chemistry.chemical_compound ,targeting delivery ,chemistry ,Folic acid ,Biochemistry ,Drug delivery ,Cancer cell ,DNA ,Biotechnology - Abstract
Introduction: Gene therapy is a recently introduced method for treatment or prevention of genetic disorders. Nanotechnology in gene therapy would be applied to replace the currently used viral vectors by potentially less immunogenic gene carriers[1]. Non-viral vectors have presented advantages such as low toxicity, low immunoreactions and the excellent ability of being chemically modified. In this work new acrylate-based nanoparticles (NPs) were synthesized and characterized. NPs were developed in the form of both nanospheres (NSs) and nanocapsules (NCs), an innovative kind of hollow NPs with an internal cavity that can maximize the amount of absorbed and released drug[2]. Due to the fact that folic acid (FA) receptors are often present in large number on cancer cells, NPs were functionalized using FA to obtain an active targeting towards cancer cells[3]. Finally the ability of functionalized NPs to load and then release a nucleic acid was investigated. Materials and Methods: Polymeric NSs and NCs were synthesized by radical polymerization starting from a diluted solution of monomers in the presence of a cross-linker. Secondly, NPs were functionalized by surface modification with FA. Absorption of a model molecule of DNA was carried out and release tests were performed. NPs were characterized by SEM, DLS, FT-IR and HPLC. In vitro cytotoxicity of NPs was investigated by MTT assay and cell uptake tests were performed to evaluate the internalization of NPs into cells. Results: SEM analysis showed a spherical shape and nanometric dimensions of the NPs, also confirmed by DLS. FT-IR analysis confirmed the obtainment of a hollow structure (NCs), the copolymer composition and the successful of surface functionalization with FA. HPLC analysis showed a good encapsulation efficiency for both NSs and NCs with an increased amount of absorbed DNA into NCs. Drug release tests pointed out an elevated initial release and a subsequent slower but prolonged delivery. A more controlled delivery profile was observed for NCs. MTT test indicated no toxic effects of the NPs on the 3T3 cells. Discussion: The production of NPs with a hollow structure allowed the maximization of the amount of absorbed DNA and a more prolonged and controlled release respect to NSs. This could be due to the fact that DNA inside the cavity needs much more time to diffuse through the polymeric matrix and be delivered. The advantage is that a higher amount of drug could be administrated using a lower amount of polymer. The method of functionalization allowed to modify the surface of both kinds of NPs without altering neither the DNA release profiles or the cytocompatibility of the nanosystems. Conclusion: The results obtained in this study showed that acrylate-based NPs could be able to interact with oligonucleotidic drugs thus working as carriers suitable for the delivery of nucleic acid. References: [1] I.M. Verma et al, Gene therapy: twenty-first century medicine, Annual Review of Biochemistry 2005; 74:711-38 [2] G.D. Fu et al, Hollow polymeric nanostructures-Synthesis, morphology and function, Progress in Polymer Science 2011; 36: 127-67 [3] J.H. van Steenis et al, Preparation and characterization of folate-targeted pEG-coated pDMAEMA-based polyplexes, Journal of Controlled Release 2003; 87: 167-76
- Published
- 2016