DNA or RNA-based non-viral therapy methods (including chemical or physical approaches) have been developed to serve as favorable alternative in cancer therapy to their virus-mediated counterparts while still suffer some unsatisfied performance (e.g., low cellular uptake, high cytotoxicity, and/or low efficiency). We hypothesize that the combination of some of these methods could improve therapy performance. Specifically, we evaluated two novel therapeutic strategies. In strategy I, gold nanoparticles (AuNPs) were used to enhance electroporation-based delivery of DNA (e.g., pGFP & pLuc) and RNA probes (e.g., miR29b): free AuNPs of high conductivity help reduce the electroporation solution resistance so that the pulse strength on cells is enhanced; transferrin grafting AuNPs (Tf-AuNPs) were brought to leukemia cell membrane through affinity binding with TfR receptors and served as virtual microelectrodes to locally polarize cells from various sites, each affected only limited area. The enhancement was found dependent on the size, concentration, and the mixing ratio of free AuNPs/Tf-AuNPs. An equivalent mixture of free AuNPs and Tf-AuNPs exhibited the best enhancement with the transfection efficiency increased 2-3 folds at minimum sacrifice of cell viability. In strategy II, polyplex (e.g., polyethylenimine-DNA or-RNA complex) were internalized through electroporating the leukemia cells after conjugating with AuNPs. The formed Au-NPs-polyplex complex became more uniform in size and less toxicity as cationic polymers were fixed on the surface of AuNPs. Electroporation helps directly introduce nanoparticles into the cell cytoplasm, avoiding slow and inefficient internalization routes like endocytosis. We found that AuNP polyplex showed significant enhancement on the transfection efficiency while no obvious increase of toxicity. These new delivery strategies, the combination of nanoparticles and electroporation technologies, may stimulate in vitro and in vivo delivery of various DNA/RNA probes, anticancer drugs, or other therapeutic materials.

Gold nanoparticle-polyplex enhanced electroporation-based therapeutic strategies in leukemia

247th National Meeting (2014)

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