Plasmid DNA microgels for drug/gene co-delivery: A promising approach for cancer therapy

Abstract

Plasmid DNA (pDNA) was efficiently encapsulated into biocompatible microgels by an inverse microemulsion polymerization method using ethylene glycol diglycidyl ether (EGDE) as cross-linker. Plasmid DNA and an anticancer drug, doxorubicin (DOX), could both be loaded with high encapsulation efficiency and released from pDNA microgels; quite relevant is also the less toxic effect of the incorporated drug, as compared with naked DOX. Photodisruption of microgels can be used as a strategy to enhance release. Mathematical models were applied to fully characterize the pDNA and drug release profiles, after light irradiation and at dark conditions; significant differences were find between the two conditions. As demonstrated by gel electrophoresis, the released plasmid DNA was intact. Moreover, the delivery of the encapsulated pDNA shows the capability of cell internalization and transfection in vitro resulting in the expression of the p53 protein. Additionally, a fluorymetry analysis demonstrated sustained pDNA release with microgels. The effect of this system on cell viability inhibition was evaluated in cancer Hela cells. The treatment with a pDNA/doxorubicin loaded microgel improves cell apoptosis. Compared with pDNA microgel or free drug, the co-delivery system has a stronger potential to suppress the development of cancer cells. We then present a quite promising pDNA based carrier that is biocompatible, photodegradable and delivers pDNA and probably different drugs, in a controlled and sustained manner; we hope this system can found interesting clinical uses, especially in the cancer treatment through a combined action of chemotherapy and gene delivery.