(186af) The Effects of Scavenger Receptor Class B Type 1 on the Uptake of Both Hard and Soft Nanoparticles

As medicine becomes more advanced, the inclusion of nanoparticles in drug delivery systems will become increasing popular. A question that needs to be answered is the how metabolic state of the patient will affect how the biodistribution of the nanoparticles. In western society, this is often associated with obesity. Obesity causes many shifts in a patient’s metabolic states, including a higher ratio of LDLs (bad cholesterol) to HDLs (good cholesterol). HDLs are said to be good cholesterol because they allow cholesterol to be brought back to the liver for clearance. Because the standard model for obesity (ob/obmice) don’t exhibit the same shift in cholesterol ratios as humans, we generated a high cholesterol model by knocking out scavenger receptor class B type 1 (SR-B1). SR-B1 binds HDLs at the liver. SR-B1 has been previously shown to also affect the uptake of HDL coated silver NPs and connected to the macrophage activation marker CD-86. To test if SR-B1 also has the ability to affect the uptake of uncoated HDLs, we conducted in vitro tests with hard NPs (polystyrene (PS)) and soft, filomicelle NPs (PBD-b-PEO). The filomicelles were selected because they are known to have weak affinities for plasma proteins. On the other hand, PS-COOH NPs to have sub micromolar affinities for HDLs. Nanoparticle uptake assays were conducted with and without a SR-B1 inhibitor (BLT-1) for a microphage (RAW 264.7) and an epithelial liver (Hep G2) cell line. Regardless of pre-incubation with mouse plasma, BLT-1 treatment resulted in a 3-fold decrease in PS-COOH and filomicelle uptake in RAW. Hep G2 cells didn’t uptake a significant amount of either NP in any condition. This shows that SR-B1 may have impacts on nanoparticle-based drug delivery beyond HDL targeting, as previously thought.