Use of Core-Cross-Linked Polymeric Micelles Induced by the Selective Detection of Cu(II) Ions for the Sustained Release of a Model Drug

A well-defined amphiphilic phenylthiosemicarbazone-based block copolymer was successfully synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, followed by postpolymerization modification. Poly( N,N-dimethylacrylamide) (pDMA) was synthesized via RAFT polymerization of N,N-dimethylacrylamide (DMA). The resulting pDMA macrochain transfer agent was further extended using 3-vinylbenzaldehyde (VBA) to yield the poly[( N,N-dimethylacrylamide)- b-(3-vinylbenzaldehyde)] [p(DMA- b-VBA)] block copolymer. The aldehyde groups of p(DMA- b-VBA) were then made to react with 4-phenylthiosemicarbazide to yield the target block copolymer poly{ N,N-dimethylacrylamide- b-[ N-phenyl-2-(3-vinylbenzylidene)hydrazine carbothioamide]} [p(DMA- b-PVHC)]. p(DMA- b-PVHC) self-assembled in aqueous solution to yield polymeric micelles that comprise a pDMA block that forms a hydrophilic shell and a pPVHC block that forms a hydrophobic core. p(DMA- b-PVHC) micelles can detect Cu(II) ions which can be determined by a color change from colorless to yellow induced by the formation of coordination complexes between Cu(II) ions and the phenylthiosemicarbazone units of p(DMA- b-PVHC). As Cu(II) ions slowly penetrated the core of p(DMA- b-PVHC) micelles, these cores cross-linked with each other, which in turn resulted in the micelle particles swelling in water. Upon the addition of Cu(II) ions to a solution of p(DMA- b-PVHC) micelles encapsulating the hydrophobic model drug coumarin 102, this drug was released from the micelles in a sustained manner due to the gradual swelling of the cross-linked micelle cores caused by the slow penetration of Cu(II) ions.