Nanoparticle personalized biomolecular corona: implications of pre-existing conditions for immunomodulation and cancer

Shaw, Jacob; Pearson, Ryan M.

doi:10.1039/d2bm00315e

Cited by 7 publications

(1 citation statement)

References 81 publications

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“…However, our results differed from previously reported results for LNPs that showed that p K a values around 9 led to increased lung selectivity, whereas the p K a for the polymers used in our studies were ≤5 (Figure S6). Several factors may play a role in the observed differences between our findings and LNPs, including differential uptake and trafficking mechanisms (Figure ), differential protein corona fingerprints, and other physicochemical properties including size and zeta potential. , Taken together, these results support that the physicochemical properties of polyMDET-C4/mRNA and polyMDET-C6/mRNA polyplexes played a major role in determining the lung selectivity of FLuc expression.…”

Section: Resultssupporting

confidence: 64%

Excipient-Free Ionizable Polyester Nanoparticles for Lung-Selective and Innate Immune Cell Plasmid DNA and mRNA Transfection

Chakraborty

Dharmaraj

Truong

et al. 2022

ACS Appl. Mater. Interfaces

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Extrahepatic nucleic acid delivery using polymers typically requires the synthesis and purification of custom monomers, post-synthetic modifications, and incorporation of additional excipients to augment their stability, endosomal escape, and in vivo effectiveness. Here, we report the development of a single-component and excipient-free, polyester-based nucleic acid delivery nanoparticle platform comprising ionizable N-methyldiethanolamine (MDET) and various hydrophobic alkyl diols (Cp) that achieves lung-selective nucleic acid transfection in vivo. PolyMDET and polyMDET-Cp polyplexes displayed high serum and enzymatic stability, while delivering pDNA or mRNA to "hard-to-transfect" innate immune cells. PolyMDET-C4 and polyMDET-C6 mediated high protein expression in lung alveolar macrophages and dendritic cells without inducing tissue damage or systemic inflammatory responses. Improved strategies using readily available starting materials to produce a simple, excipient-free, non-viral nucleic acid delivery platform with lung-selective and innate immune cell tropism has the potential to expedite clinical deployment of polymer-based genetic medicines.

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Section: Resultssupporting

confidence: 64%