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Biomaterials

Biomaterials - Poster Session E

Poster P2 - Understanding the bone marrow targeting of biomimetic nanoparticles in inflammaging

Saturday, October 26, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Inflammation in aging, termed as “inflammaging”, is an inflammatory process that significantly impacts the typical features of hematopoiesis in the mid-aged and elderly [1]. Age-induced inflammation regulates the proliferation of hematopoietic stem and progenitor cells (HSPCs) by initiating the inflammatory immune response. HSPCs also exhibit dysfunctional changes during aging and have altered interactions with the bone marrow niche, making them a key focus of research. There is significant interest in developing nanoparticles that can target HSPCs in hematopoietic disorders, yet it is not known how inflammaging affects the ability of nanoparticles to reach the bone marrow and target HSPCs. In this work, the impact of age-induced inflammation on the biodistribution of HSPC-targeted megakaryocyte membrane-wrapped nanoparticles (MkNPs) is studied by intravenously injecting the MkNPs into mice of different age groups (10-, 30-, or 60-week) and evaluating accumulation in bone marrow and other organs with fluorescent imaging techniques.

Materials and

Methods:  C57BL/6 female mice of different age groups (10-, 30- and 60-week) were purchased from Jackson laboratory. To perform in vivo biodistribution studies, we synthesized megakaryocyte cell membrane wrapped polymeric nanoparticles (MkNPs) as previously described [2] and injected them intravenously via tail vain into mice of different age groups. Mice injected with saline were used as controls in all the experiments unless stated otherwise. At ~16 hours post administration, mice of all three age groups were euthanized, and organs were harvested for ex-vivo IVIS imaging. Femurs were used for flow cytometry analysis and other organs were fixed in 4% PFA for ex-vivo fluorescence imaging, immunostaining, and histology studies. Flow cytometry was performed to determine the HSPC targeting ability of MkNPs. IVIS imaging was used to visualize the biodistribution of MkNPs in various organs while fluorescence imaging was used for the quantification of MkNPs at the femoral bone marrow. All applicable protocols, animal handling, surveillance, and experimentation were performed in accordance with the Institutional Animal Care and Use Committee.

Results, Conclusions, and Discussions: MkNPs were synthesized using our previously published protocol [2] and displayed uniform core-shell structure in TEM imaging (Figure 1a). Particle size and zeta potential of MkNPs were ~160 nm and -24.6 mV, respectively. After successful synthesis, MkNPs or saline were injected to mice of different age groups (Figure 1b). Ex vivo IVIS imaging demonstrated an increased radiant efficiency of MkNPs in liver and spleen of 10-week mice among all the three groups. Interestingly, MkNPs showed higher retention in the femoral bones of 10-week and 60-week old mice as compared to 30-week old mice (Figure 1c). Flow cytometry results showed higher HSPC labelling with MkNPs in 60-week mice. Finally, ex vivo confocal microscopy confirmed a higher level of MKNPs was present in the femoral bone marrow of 10- and 60-week-old mice compared to 30-week old mice, corroborating the IVIS results (Figure 1d). Collectively, these results indicate that MkNP biodistribution, femoral accumulation, and HSPC targeting are impacted by inflammaging.

Acknowledgements (Optional):