Comparison of the siRNA and mRNA Carrying Capacity of Quaternary Ammonium β-Cyclodextrin Polymer and Polyethylenimine

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Abstract
Background/Objectives: Intracellular delivery of RNA molecules is challenging. To solve this problem, many carrier systems are available, which are based on liposomes or polymers. Cyclodextrins are widely used excipients to increase the solubility of small molecules, but their polymer derivatives are able to deliver macromolecules. In the present study, we aimed to investigate and compare the siRNA and mRNA carrying capacity of a cationic quaternary ammonium β-cyclodextrin polymer (QABCDPS) and polyethylenimine (PEI). Methods: Cytotoxicity of the polymers was tested by the MTT method. Polyplexes were formulated with different nitrogen/phosphate ratios (NP), and their physicochemical properties were examined using dynamic light scattering and zeta potential measurements. Cellular internalization and intracellular effects of the polyplexes were investigated by confocal microscopy and flow cytometry. Results: QABCDPS exhibited lower toxicity compared to PEI, effectively binding both siRNA and mRNA and delivering them into vesicles in the cytoplasm, but showing different internalization patterns. Polyplexes formed with PEI showed stronger biological effect than those with QABCDPS, which can be attributed to the strength of interactions facilitated by the polymers. Conclusions: In summary, QABCDPS is a low-toxicity carrier that shows some promise for mRNA delivery but is ineffective for siRNA silencing under the tested conditions and requires further structural optimization.
Funding Information
  • National Research, Development and Innovation Office (OTKA K146028)
  • National Research, Development and Innovation Office (FK 124634)
  • National Research, Development and Innovation Office (OTKA K147308)
  • National Research, Development and Innovation Office (NKFIH-143360)
  • Ministry of Culture and Innovation of Hungary (TKP2021-EGA-18)
  • National Research, Development and Innovation Office (TKP2021-EGA)

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