DNA Origami Agent Tackles Cancer Resistance

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Researchers from the National Center for Nanoscience and Technology, China, have engineered a nanoplatformthat selectively delivers small hairpin RNA transcription templates and chemotherapeutics into multidrug-resistant tumors”. The procedure allows the deadly cocktail of gene-silencing elements and cytostatic drugs to effectively destroy the cancerous cells.

The mutated cells that form tumors can develop a tolerance to any anticancer drug through numerous mechanisms, decreased drug uptake, increased drug efflux, activation of detoxifying systems, activation of DNA repair mechanisms, evasion of drug-induced apoptosis, etc. There are numerous genes for proteins that can remove the medication from the cells well before it can activate.

One solution is to interfere at a gene expression level, using RNA interference (RNAi) techniques: small RNAi strands combine with messenger RNA and inhibit transcription. The only issue is these templates need to be delivered directly into the cytoplasm of the cell. This is where the DNA origami technique comes into play.

Baoquan Ding, Ph.D, leads the team that constructed a nanosized DNA structure that can bind to multiple functional units and includes a hydrophobic potent drug doxorubicin (DOX). The system performed remarkably well, killing the tumors but leaving healthy tissue undamaged.

The study notes how the nanostructure “not only specifically targets cancer cells, thus reducing severe side effects in chemotherapy, but also carries a drug and everything needed to suppress resistance in the cell when releasing the drug”.

These results open the way for a completely new strategy for the treatment of multidrug‐resistant tumors. The platform is easily modifiable and can be adapted for a wide variety of therapeutic uses.

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