Physical forms of microparticles and nanoparticles, such as the size, charge, and shape, are known to affect endocytosis. Improving the physical designs of the drug carriers can increase the drug uptake efficiency and the subsequent drug efficacy. Simple shapes, such as sphere and cylinder, have been studied for their ability for endocytosis. To have a better understanding of the shape effect on cellular uptake, different particle shapes were prepared, using the keyboard character shapes, and their impacts on cellular uptake were examined. The results showed that shapes with higher aspect ratio and sharper angular features have a higher chance of adhering to the cells and become internalized by the cancer cells. The local interaction between the cell membrane and the part of the microparticle in contact with the cell membrane also plays a crucial role in determining the outcome.

No abstract

Adenosine is widely thought to elicit coronary vasodilation and attenuate smooth muscle proliferation, thereby providing cardioprotection. We cloned the porcine adenosine A1 receptor (A1R) subtype and found that it paradoxically stimulated proliferation of cultured coronary smooth muscle cells by extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) signaling pathways, thus suggesting A1R dysregulation could play a role in coronary in‐stent restenosis. We utilized the Ossabaw swine model of metabolic syndrome (MetS) to test the hypothesis that A1R up‐regulation and A1R‐ERK1/2 signaling play a role in the development of coronary in‐stent stenosis in MetS. Intracoronary stent deployment followed by different durations of recovery from stenting showed A1R upregulation occurred before maximal amount of in‐stent stenosis. Swine were fed standard chow (Lean) or excess calorie atherogenic diet for over 20 weeks, which elicited MetS characteristics. We observed reduced coronary in‐stent stenosis by TAXUS (paclitaxel‐eluting) stents in MetS. Selective A1R antagonism with DPCPX‐eluting stents decreased coronary ERK1/2 activation and decreased in‐stent stenosis comparable to TAXUS. Conclusion: A1R upregulation and A1R‐ERK1/2 activation contributes to coronary in‐stent stenosis in vivo in the setting of MetS. Support: NIH RR013223, HL062552, Purina TestDiet to MS; HL078715 to KP; AHA to XL.Grant Funding Source: NIH