Three monofunctional copolymers into one multifunctional Micelle: Part 1. Preparation and properties

In the present work, we propose a new multifunctional micelle, co-self-assembled from different monofunctional copolymers, for tumor targeting and fluorescent and electron spin resonance (ESR) dual detection. Firstly, a poly(D,L-lactic acid)-b-poly(N-isopropyl methacrylamide-co-N-isopropylmaelic acid-co-10-undecenoic acid)-b-poly(N-acryloxysuccinimide) (PLA-PNNUA-PNAS) copolymer, with pH-dependent thermo-responsive properties, was synthesized. The copolymer was synthesized using reversible addition fragmentation chain transfer (RAFT) polymerization method, after which it was further used as a parent copolymer to combine with folic acid (FA), fluorescein isothiocyanate (FITC) and 4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl (4-NH2-TEMPO), respectively, resulting into three new monofunctional copolymers. Finally, the multifunctional copolymer micelle was easily then fabricated, through co-self-assembly, using the monofunctional copolymers. The results from in vitro cell assays indicated that the proposed micelle was able to provide desired multifunctional properties, including tumor specific targeting and fluorescent and ESR dual detection. Additionally, the parent copolymer allowed conjugation with other ligands to prepare them for more functional copolymers attachment for future potential applications. More importantly, the multifunctional properties of the copolymer micelles could be rationally tailored, able for given purposes.