Ref.: MpoSi32-004

Thiol-ene click chemistry: a feasible approach for covalent conjugation of polyester nanoparticles with folic acid to design nanocarriers for targeted delivery

Apresentador: Heloísa Bremm Madalosso

Autores (Instituição): Madalosso, H.B.(Universidade Federal de Santa Catarina); Sayer, C.(Universidade Federal de Santa Catarina); Guindani, C.(Universidade Federal do Rio de Janeiro); Araújo, P.H.(Universidade Federal de Santa Catarina); da Silva, L.C.(McGill University); Landfester, K.(Max Planck Institute for Polymer Research);

Resumo:
Thiol-ene click chemistry is modular, stereospecific, environmentally friendly, broad in scope, and highly yielding reaction with an absence of byproducts, where a thiol and an akene group are coupled forming a covalent bond [1]. This reaction has been widely studied to covalently attach biomolecules and amino acids on unsaturated polymer chains in order to modify the polymer’s chemical and biological properties for specific applications. Polyester nanoparticles (NPs) have been utilized as specific nanocarriers to deliver therapeutic and diagnostic agents. However, some drawbacks such as the interaction of these NPs with innate immune cells and their uptake by the mononuclear phagocyte system of the spleen, liver, and lung have compromised their specificity [2]. These challenges could be overcome through bioconjugation strategies, where bioactive molecules, such as folic acid (FA), are introduced on the polymeric chains, increasing the targeting efficiency [3]. Folate receptors are overexpressed in cancer cells, making folic acid a suitable molecule to develop drug delivery systems focused on targeting cancer cells, once it is internalized by the cells via receptor-mediated endocytosis. Herein, we report a feasible and quick strategy to conjugate novel copolyester NPs with folic acid via thiol-ene click chemistry. Poly(globalide-co-?-pentadecalactone) (PGlPDL) is synthesized via miniemulsion copolymerization, enzymatically catalyzed with Candida Antarctica B (CALB), and bioconjugated with Folate-PEG-SH using a photoinitiator. NPs with a size of 140 nm were obtained with monomer conversions of 95.5%, with a number average molecular weight of 1660 g/mol, a polydispersity of 2.9, and a melting temperature of 66.5 °C. The number of available double bonds for bioconjugation was determined via NMR. The bioconjugation efficiency with Folate-PEG-SH was evaluated via UV-spectroscopy (283 nm), indicating 99.3% of double bond consumption. The development of this easy and quick strategy to conjugate biomolecules and polyester NPs is capable of tuning the specificity of the nanocarriers. These PGlPDL-FA NPs represent promising alternatives to design nanocarriers for targeting delivery in cancer cells, potentially benefiting from a stealth effect facilitated by the PEG component embodied in the Folate-PEG-SH chemical structure. References [1] C. E. Hoyle, T. Y. Lee and T. Roper, J Polym Sci A Polym Chem, 2004, 42, 5301–5338. [2] H. Banu, D. K. Sethi, A. Edgar, A. Sheriff, N. Rayees, N. Renuka, S. M. Faheem, K. Premkumar and G. Vasanthakumar, J Photochem Photobiol B, 2015, 149, 116–128. [3] M. Sajjad, M. I. Khan, S. Naveed, S. Ijaz, O. S. Qureshi, et al., AAPS PharmSciTech, 2019, 20.