Switchable conformational changes of DNA nanogel shells containing disulfide-DNA hybrids for controlled drug release and efficient anticancer action

摘要

Oligonucleotide strands containing dithiol (-SS-) groups were used as the co-crosslinkers in PNIPA-AAc based nanogels (NGs). They hybridized with PEG-oligonucleotides introduced into the gels. The specific DNA hybrid formed in the nanogel/nanocarrier was involved in highly efficient accumulation of intercalators. The presence of -SS- groups/bridges improved the storing efficiency of doxorubicin (Dox) in DNA hybrids by 53, 40 and 20% compared to regular, single stranded and regular double stranded DNA crosslinkers, respectively. The explicit arrangement of the hybrids in the carrier enabled their reduction by glutathione and an effective cancer treatment while the side toxicity could be reduced. Compared to the NGs with traditional crosslinkers and those containing typical dsDNA-based hybrids, an improved, switchable and controlled drug release occurred in the novel NGs. Since the novel NGs can release the oligonucleotide strands during their degradation, this gives an opportunity for a combined drug-gene therapy.