Polycationic Nanogels for the Targeted Delivery of Micrornas

In the last few years, microRNA (miRNA) therapy has been proposed as a means to suppress tumorigenesis in cancer patients^1–3. However, targeted delivery of miRNA remains a barrier for further implementation of this therapeutic strategy⁴. The tumor microenvironment differs markedly from the normal cell environment due to hypoxic regions around tumor cells. These regions of lowered oxygen and increased glycolysis result in local acidification⁵. In the present research, we have designed a novel targeted miRNA delivery system that utilizes pH-responsive polycationic nanogels. These polycationic carriers remain collapsed in basic and neutral conditions but are triggered by a change in local pH that would result in carrier swelling and associated miRNA release. Polycationic nanogels are synthesized via the controlled polymerization technique ARGET ATRP. Nanogels are then characterized and analyzed using Fourier transform infrared spectroscopy to characterize their chemical structure, dynamic light scattering to establish the carrier particles size distribution, and potentiometric titration to identify particle pH-responsiveness. Preliminary results of this work indicate that the nanogels exhibit favorable swelling behavior. These results suggest that this polycationic nanogel system is a promising system for miRNA delivery and potentially therapy.

This research was supported by grant No. R01-EB022025 from the National Institutes of Health.

References:

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[3] Zeng et al. (2017), Molecular Pharmaceutics, 14(1), 81-92.

[4] Hosseinahli et al. (2018), Journal of Cellular Physiology, 233(8), 5574-5588.

[5] Boedtkjer and Pedersen (2020), Annual Review of Physiology, 82(1), 103-126.