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bioRxiv · 10.1101/2025.06.01.657318

Mesenchymal Stem Cell Membrane Coating of Gelatin Nanospheres with Drug Release Ability for Inflammatory Tissue Targeting

Moriyama, K.·Ando, M.·Sakurai, K.·Sakurai, I.·Tabata, Y.
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Abstract

Improvements in drug delivery have been achieved using nanospheres to prolong drug efficacy, accelerate absorption, and target tissues with ongoing inflammation. Although nanospheres have numerous pharmacokinetic advantages their tissue-targeting ability is poor. In contrast, mesenchymal stem cells (MSC) accumulate in high numbers in inflammatory tissues via the interaction between CXC-chemokine receptor 4 (CXCR4) expressed on MSC and stromal cell-derived factor 1 (SDF-1) secreted during inflammation. Therefore, this study investigated coating gelatin nanospheres (GNS) with MSC membranes (MSC-GNS) by extrusion and ultrasonication methods to enhance their inflammatory tissue tropism. {zeta}-potential measurements, western blotting and single-particle analysis of MSC-GNS by flow cytometry demonstrated the GNS surface was successfully coated with MSC membranes. Dot blotting demonstrated the binding ability of CXCR4 for SDF-1 was retained by MSC-GNS but absent for MSC-membrane-free GNS. The blood clearance of MSC-GNS was examined by their intravenous injection into mice. Although MSC-GNS and GNS were retained during the early distribution phase, MSC-GNS had a higher retention than GNS during the later elimination phase. Finally, we investigated the tissue distribution of MSC-GNS by intravenous injection into a mouse model of liver fibrosis and their potential therapeutic effect on liver fibrosis. We found a higher accumulation of MSC-GNS in inflamed livers and higher blood retention compared with MSC-membrane-free GNS. Furthermore, MSC-GNS loaded with an anti-fibrotic agent (LSKL, a 4-amino acid peptide that inhibits fibrosis progression) had an enhanced therapeutic effect on liver fibrosis than uncoated nanoparticles. Therefore, MSC-GNS might be a drug carrier with inflammatory tissue targeting and controlled drug release abilities. Synopsis Table of Contents Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/657318v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@12331d8org.highwire.dtl.DTLVardef@19d7b43org.highwire.dtl.DTLVardef@79591org.highwire.dtl.DTLVardef@1ec805a_HPS_FORMAT_FIGEXP M_FIG C_FIG Mesenchymal stem cell membrane coated gelatin nanosphere as DDS nanocarrier

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Moriyama, K., Ando, M., Sakurai, K., Sakurai, I., Tabata, Y.. 2025-06-03. Mesenchymal Stem Cell Membrane Coating of Gelatin Nanospheres with Drug Release Ability for Inflammatory Tissue Targeting. https://doi.org/10.1101/2025.06.01.657318

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