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Nano and Micro Technologies

Nano and Micro Technologies - Poster Session B

Poster K1 - Exploring Nanoparticle-Mediated Targeting of Adipose Stem Cells for Obesity Treatment

Thursday, October 24, 2024
2:45 PM – 3:45 PM EST
Location: Exhibit Hall E, F & G

Introduction:  Adults with obesity are in a state of chronic inflammation, which can contribute to metabolic diseases, cardiovascular disease, and insulin resistance. The application of nanoparticles to treat obesity is an innovative approach. Understanding the relationship and the uptake mechanism (e.g., endocytosis) between nanoparticles and cells in the biological systems is crucial, particularly in the context of drug development. Adipose tissue contains different cells including adipose stem cells capable of differentiating into various cell types including brown and beige adipocytes. Brown and beige adipocytes promote energy dissipation as heat and fuel thermogenesis, in contrast to white adipocytes, which have minimal mitochondria and low metabolic activity. Our goal is to use nanoparticles to increase beige adipocytes formation, thus promoting energy expenditure and reducing the impact of obesity. Nanoparticles, with their versatile pore size, particle size, and shape, have shown great promise in numerous biomedical applications. Specifically, mesoporous silica nanoparticles (MSNs) have demonstrated efficacy in delivering therapeutic drugs to cells and tissues. This research focuses on evaluating the interaction between MSNs and adipose stem cells, with the goal of developing novel adipose stem cell treatments. By targeting stem cells within adipose tissue, we can potentially generate the desirable brown and beige adipocytes while minimizing the challenges associated with manipulating differentiated cells. This approach offers a pathway to innovative nanomedicine-based treatments.

Materials and

Methods:  The synthesis method for Hexagonal Mesoporous Silica Nanoparticles (HMSNs) involves a sol gel process. Cetyltrimethylammonium bromide (CTAB) was dissolved in an ammonium hydroxide (NHâ‚„OH) solution and heated with stirring, followed by the addition of tetraethyl orthosilicate (TEOS), leading to the formation of hexagonal mesophase silica structures. The HMSNs were then coated with a liposome formulation using DPPC (skeleton lipid), cholesterol (mechanical properties), DMPG (charge), and DSPE-PEG2K to help with stability. The HMSNs were then added to human adipose derived stem cells (hADSC) and cultured together during different timepoints 3 hr, 6hr, 24 hr, and 48 hr (the cells were cultured in a 6 wells plate at 250,000 cells/well). After culturing the cells were stained with rab5 to look for colocalization of nanoparticles within the hADSC endosomes using confocal microscopy.

Results, Conclusions, and Discussions: Confocal microscopy was employed to image the samples, using Rab5 stain for endosomes, DAPI for the nucleus, and Cy3 stain for the nanoparticles. The confocal images revealed colocalization of nanoparticles within the hADSCs' Rab5-labeled endosomes and, to a lesser extent, within the nucleus. The colocalization analysis showed that nanoparticle internalization increased over different incubation times, with a distinct curve indicating time-dependent uptake. Additionally, the study examined the effects of different lipid formulations on the uptake and colocalization of the nanoparticles, revealing that certain formulations enhanced the internalization of nanoparticles into the hADSCs.

Future studies will focus on how loaded and unloaded HMSNs with Forskolin affect the interaction between HMSNs and hADSCs. Additionally, the impact of different lipid formulations on the uptake of HMSNs will be explored. Understanding the colocalization of nanoparticles within the endosomes and nucleus of hADSCs is crucial for developing new therapeutic approaches. Investigating the pathways of nanoparticle uptake, such as endocytosis, and using inhibitors to track nanoparticle presence will provide further insights. Ultimately, the main goal is to comprehend the interactions between hADSCs and nanoparticles to enhance the efficacy of nanoparticle-based treatments.

Acknowledgements (Optional):