Stimuli-responsive polyamine-DNA blend nanogels for co-delivery in cancer therapy

• Novel hydrogels have been synthesized by pDNA condensation and cross-linking.
• To enhance transfection, transferrin has been incorporated into the gels.
• The systems are photodegradable which promote the controlled release of biomolecules.
• The tumoral treatment through the dual action of drug and gene is more effective.
• This work is a great contribution for significant advances in cancer therapy.

Polyamine plasmid DNA (pDNA) hydrogels have been synthesized by an original approach which conjugates pDNA condensation by polyamines and cross-linking reaction with ethylene glycol diglycidyl ether. In an attempt to design more sophisticated vectors with enhanced transfection efficiency and targeting ability, the cell-binding ligand transferrin has been incorporated into polyethylenimine formulations. All systems are photodegradable which allows for the controlled release of different plasmids (pVAX1-LacZ and pcDNA3-FLAG-p53) and anticancer drugs (doxorubicin, epirubicin and paclitaxel). The tumoral treatment through the combined action of pcDNA3-FLAG-p53 gene and an anticancer drug has a stronger potential to suppress the development of cancer cells. The effect is greatly improved when transferrin is encapsulated into the carriers. This study is a relevant contribution for the design of novel generation of plasmid biopharmaceuticals for progresses in gene cancer therapy, feeding the hope of cancer cure.

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