A novel kind of redox-responsive polymeric drug delivery system has been designed and prepared successfully through the coupling of the multithiol branched
polymers and
thiol-containing drugs. The branched poly((S-(4-vinyl) benzyl S'-propyltrithiocarbonate)-co-(poly(ethylene glycol) methacrylate)) (poly(VBPT-co-PEGMA)) was synthesized by one-pot reaction via reversible addition-fragmentation chain transfer (RAFT) copolymerization. Subsequently, the hydrophobic
thiol-containing anticancer
drug 6-mercaptopurine (MP) was conjugated to poly(VBPT-co-PEGMA) by
thiol-
disulfide exchange reaction, resulting in the formation of poly(VBPT-co-PEGMA)-S-
S-MP conjugate. Due to its amphiphilicity, poly(VBPT-co-PEGMA)-S-
S-MP conjugate self-assembled into amphiphilic
micelles in aqueous
solution. Under a reductive environment, the disassembly of polymeric
micelles resulted in the MP release. Flow cytometry and confocal
laser scanning microscopy (CLSM) measurements demonstrated that the poly(VBPT-co-PEGMA)-S-
S-MP micelles could be taken up by Raji cells (a
Burkitt lymphoma cell line). The viability of the Raji cells incubated with the
glutathione (GSH) mediated poly(VBPT-co-PEGMA)-S-
S-MP micelles was investigated by Cell Counting Kit-8 (CCK-8) assay. The experimental results showed that the viability of the
glutathione monoester (GSH-OEt) pretreated cells was lower than that without pretreatment, while the viability of the
buthionine sulfoximine (BSO) pretreated cells was higher than that without pretreatment. The poly(VBPT-co-PEGMA)-S-
S-MP micelles could induce the apoptosis of Raji cells, and the apoptosis behavior was dose-dependent. This redox-responsive
polymer-
drug conjugate provides a promising platform for the delivery of
thiol-containing
biological molecules.