Immunogenic lipid-coated mesoporous silica nanoparticles (ILM) present pathogen-associated molecular patterns (PAMPs) on the nanoparticle surface to engage pathogen-associated receptors on immune cells. The mesoporous core is capable of loading additional immunogens, antigens or drugs. In this study, the impact of lipid composition, surface potential and intercalation of lipophilic monophosphoryl lipid A (MPL-A) in the lipid coat on nanoparticle properties and cellular interactions is presented. Loading and retention of the model antigen ovalbumin into the mesoporous silica core were found to be similar for all nanoparticle formulations, with presentation of ova peptide (SIINFEKL) by major histocompatibility complex (MHC) evaluated to facilitate the selection of an anionic nanoparticle composition. ILM were able to induce lysosomal tubulation and streaming of lysosomes towards the cell surface in dendritic cells, leading to an enhanced surface presentation of MHC. Myeloid cells robustly internalized all ILM formulations; however, non-myeloid cells selectively internalized cationic ILM in vitro in the presence of 20% serum. Interestingly, ILM administration to the peritoneal cavity of mice with disseminated ovarian cancer resulted in selective accumulation of ILM in tumor-associated tissues (>80%), regardless of nanoparticle surface charge or the presence of MPL-A. Immunofluorescence analysis of the omental tumor showed that ILMs, regardless of surface charge, were localized within clusters of CD11b+ myeloid cells 24 h post administration. Selective uptake of ILMs by myeloid cells in vivo indicates that these cells outcompete other cell populations in the ovarian tumor microenvironment, making them a strong target for therapeutic interventions.
Despite encouraging outcomes of the eight FDA approved drugs in lessening obesity burden, they have been associated with side effects caused by the lack of direct action on the adipose tissue. Therefore, a nanomedicine is reported that promotes the transformation of local fat‐storage white adipocytes, associated with obesity, into thermogenic adipocytes, indicative of enhanced metabolism, to both human cells and mice. This nanomedicine consisting of a lipid‐silica nanohybrid that allows accommodation of the natural supplement forskolin has resulted in successful browning of mature human adipocytes in vitro through upregulating thermogenesis biomarkers on mature human adipocytes and in vivo in mice tissue (achieving 400‐ and 80‐fold increases in UCP1 and Cox7A1, respectively), while significantly enhancing glucose uptake and lipolysis in an acute fashion and significantly preventing weight gain in high fat diet (60% HFD) mice compared to other treatments including liposomal medicine.
4 October 2025 in International Journal of Pharmaceutics