RESUMEN
In this study, six-arm star-shaped poly(N-vinylcaprolactam) (PNVCL) polymers prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization were subjected to aminolysis reaction using hexylamine. Chemically crosslinked gels or highly end-functionalized star polymers can be obtained depending mainly on the type of solvent used during the transformation of the RAFT functional group. An increase in the viscosity of the solution was observed when the aminolysis was carried out in THF. In contrast, when the reaction was conducted in dichloromethane, chain-end thiol (PNVCL)6 star polymers could be obtained. Moreover, when purified (PNVCL-SH)6 star polymers are in contact with THF, the gelation occurs in just a few minutes, with an obvious increase in viscosity, to form physical gels that become chemically crosslinked gels after 12 h. Interestingly, when purified (PNVCL-SH)6 star polymers were stirred in distilled water, even at high aqueous solution concentration (40 mg/mL), there was no increase in the viscosity or gelation, and no evident gels were observed. The analysis of the hydrodynamic diameter (Dh) by dynamic light scattering (DLS) did not detect quantifiable change even after 4 days of stirring in water. On the other hand, the thiol groups in the (PNVCL-SH)6 star polymers were easily transformed into trithiocarbonate groups by addition of CS2 followed by benzyl bromide as demonstrated by UV-Vis spectroscopical analysis and GPC. After the modification, the (PNVCL)6 star polymers exhibit an intense yellow color typical of the absorption band of trithiocarbonate group at 308 nm. To further demonstrate the highly effective new trithiocarbonate end-functionality, the PNVCL polymers were successfully chain extended with N-isopropylacrylamide (NIPAM) to form six-arm star-shaped PNIPAM-b-PNVCL block copolymers. Moreover, the terminal thiol end-functionality in the (PNVCL-SH)6 star polymers was linked via disulfide bond formation to l-cysteine to further demonstrate its reactivity. Zeta potential analysis shows the pH-responsive behavior of these star polymers due to l-cysteine end-functionalization. By this using methodology and properly selecting the solvent, various environment-sensitive star polymers with different end-groups could be easily accessible.
RESUMEN
In the present study, poly(ethylene glycol)-b-poly(N,N-diethylaminoethyl methacrylate) (PEG-b-PDEAEM) amphiphilic block copolymers were synthetized by reversible addition-fragmentation chain transfer (RAFT) polymerization using two different macro chain transfer agents containing PEG of 2000 and 5000 g/mol and varying the length of the PDEAEM segment. From the obtained block copolymers, polymersome type nanometric aggregates were obtained by two different techniques. By direct dispersion, particle diameters around 200 nm were obtained, while by solvent exchange using THF and water, the obtained diameters were around 100 nm. These block copolymers were used to encapsulate gold nanorods and doxorubicin (DOX) with good efficiencies to obtain nanomaterials with potential use as dual stimuli-sensitive drug delivery systems for combined anticancer therapies. Drug delivery studies showed that the release rate of DOX was accelerated when the pH was lowered from 7.4 to 5.8 and also when the systems were irradiated with a NIR laser at pH 7.4. The combination of lower pH and near infrared (NIR) irradiation resulted in higher drug release only in the case of polymersomes with lower molecular weight PEG.