Safe and efficient delivery of biomolecules (such as large plasmids, DNA and small interfering RNA) into living cells holds great promise for treating diseases such as cancer. Despite the promising potential of DNA-based therapeutics, their delivery is still challenging because highly negative charged biological molecules have difficulty crossing the cell membrane and are prone to degradation prior to cellular uptake in physiological conditions.
So far, biologists have approached the problem by packaging DNA or RNA inside nanoscale vectors (carriers) to enhance their resistance to enzymatic degradation, and to assist cellular entry. Viral vectors offer very high transducing efficiency, but their application in humans raises many safety concerns due to their toxicity, random uptake, the risk of immune response and potential replication. In recent years, synthetic nanoparticles called non-viral vectors have emerged as a safer alternative to viral vectors. However, the cellular uptake of these nanoparticles occurs through the endocytosis process. After internalization, the entrapment of lipoplex nanoparticles into endocytic vesicle is a major barrier, which limits the efficacy of lipoplex nanoparticles in achieving gene silencing and expression and even there can be potential toxic side effects.
Scientists from Delft, Ohio State and Duke University have now found a safe and efficient way to deliver nanoparticles containing a wide range of biomolecules into living cells without going through the endocytosis route, by applying electrical pulses through a nanochannel. The approach effectively facilitates the cellular uptake and release of siRNAs, DNAs and large plasmids from nanoparticles. This nanofluidic device has the ability to produce a highly localized and focused electric field on a small area of the cell membrane adjacent to the nanochannel. This treatment induces a strong electrophoresis at the nanoscale leading to drive and inject exogenous cargo instantly into the single cells during poration.