Mymetics Corp (MYMX)

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Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice

Publication Date:March 1, 2021

Fig 8 is getting close to the fig in the Mymx presentation

https://pubs.acs.org/doi/10.1021/acsnano.0c08384

With a particle size of around 280 nm, the avidin-capped MSNs are too large to be drained with the interstitial flow to the lymph nodes and thus create a small depot at the injection site. By taking advantage of patrolling migratory DCs that take up foreign material such as nanoparticles, become activated, migrate to the closest lymph nodes, and initiate the immune response there, a major drawback of smaller particles can be avoided. Smaller particles distribute more quickly in the lymphatics and can also enter the bloodstream, where they are subject to clearance by the liver, kidneys, or spleen.(72) This may lead to unwanted toxic side effects and a much faster turnover of the delivered drug.

https://pubmed.ncbi.nlm.nih.gov/23626707/

72

Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice
Kourtis, Iraklis C.; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A.; Swartz, Melody A.
PLoS One (2013), 8 (4), e61646CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)
Nanoparticles were extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biol. and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunol. response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to i.m. administration, leading to ~50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with esp. strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma.