Solvent-Free Synthesis of Multifunctional Block Copolymer and Formation of DNA and Drug Nanocarriers

Abstract

The synthesis of well-defined multifunctional polymers is of great importance for the development of complex materials for biomedical applications. In the current work, novel and multi-amino-functional diblock copolymer for potential gene and drug delivery applications was successfully synthesized. A highly efficient one-step and quantitative modification of an alkyne-functional polycarbonate-based precursor was performed, yielding double hydrophilic block copolymer with densely grafted primary amine side groups. The obtained positively charged block copolymer co-associated with DNA, forming stable and biocompatible nanosized polyplexes. Furthermore, polyion complex (PIC) micelles with tunable surface charge and decorated with cell targeting moieties were obtained as a result of direct mixing in aqueous media of the multi-amino-functional block copolymer and a previously synthesized oppositely charged block copolymer bearing disaccharide end-group. The obtained well-defined nanosized PIC–micelles were loaded with the hydrophobic drug curcumin. Both types of nanoaggregates (polyplexes and PIC–micelles) were physico-chemically characterized. Moreover, initial in vitro evaluations were performed to assess the nanocarriers’ potential for biomedical applications.

Keywords

• multifunctional
• block copolymer
• thiol-yne click
• polyplex
• polyion complex micelle
• DNA