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bioRxiv · 10.1101/2024.07.26.605135

Efficient internalization of poly(benzyl malate) and poly(ethylene glycol)-b-poly(benzyl malate) copolymer based nanoparticles by human hepatic HepaRG cells and macrophages : Impact of nanoparticle functionalization by GBVA10-9 peptide on cell uptake.

NAHAS, H.·SABA, S.·METLEJ, P.·RIBAULT, C.·VENE, E.·LEPAREUR, N.·CAMMAS-MARION, S.·LOYER, P.
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Abstract

In the past years, we have designed biodegradable poly(benzyl malate) (PMLABe73) homopolymer and amphiphilic poly(ethylene glycol)-b-PMLABe (PEG42-b-PMLABe73) copolymer and several modified (co)polymers to produce biocompatible polymeric nanoparticles (NPs) capable of targeting hepatic cells in vitro with the goal to develop applications in the treatment of liver diseases. The current study aimed at comparing the uptake of PMLABe73 PEG42-b-PMLABe73-based NPs in human hepatic HepaRG cells, primary macrophages and peripheral blood mononuclear cells (PBMC). The uptake of NPs prepared from PEG42-b-PMLABe73 was significantly lower than that of PMLABe73 in both hepatic cells and macrophages. In addition, the NPs uptake by HepaRG cells was inversely correlated to the density of PEG present on their surface. In contrast, the internalization of with PMLABe-based NPs by human macrophages was not affected by low PEG densities, only uptake of fully pegylated PEG42-b-PMLABe73based-NPs was significantly decreased. Herein, we also showed that PMLABe-based NPs did not strongly accumulated in PBMC, T lymphocytes and neutrophils while monocytes showed slightly higher uptake of these NPs. Moreover, we further demonstrated that PMLABe-derived NPs by did not trigger inflammasome activation and secretion of pro-inflammatory cytokines neither in macrophages nor HepaRG cells. Then, we demonstrated that peptide GBVA10-9 derived from George Baker (GB) Virus A, known to exhibit a good hepatotropism did not significantly affect the uptake of PMLABe73-based NPs in HepaRG cells and macrophages, when grafted onto these NPs. The present results demonstrate that PMLABe-derived NPs are very efficiently internalized in both macrophages and hepatocytes but not in PBMC and reinforce our previous reports regarding their biocompatibility.

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NAHAS, H., SABA, S., METLEJ, P., RIBAULT, C., VENE, E., LEPAREUR, N., CAMMAS-MARION, S., LOYER, P.. 2024-07-26. Efficient internalization of poly(benzyl malate) and poly(ethylene glycol)-b-poly(benzyl malate) copolymer based nanoparticles by human hepatic HepaRG cells and macrophages : Impact of nanoparticle functionalization by GBVA10-9 peptide on cell uptake.. https://doi.org/10.1101/2024.07.26.605135

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