7 research outputs found
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On the near-wall accumulation of injectable particles in the microcirculation: smaller is not better
Although most nanofabrication techniques can control nano/micro particle (NMP) size over a wide range, the majority of NMPs for biomedical applications exhibits a diameter of ~100 nm. Here, the vascular distribution of spherical particles, from 10 to 1,000 nm in diameter, is studied using intravital microscopy and computational modeling. Small NMPs (≤100 nm) are observed to move with Red Blood Cells (RBCs), presenting an uniform radial distribution and limited near-wall accumulation. Larger NMPs tend to preferentially accumulate next to the vessel walls, in a size-dependent manner (~70% for 1,000 nm NMPs). RBC-NMP geometrical interference only is responsible for this behavior. In a capillary flow, the effective radial dispersion coefficient of 1,000 nm particles is ~3-fold larger than Brownian diffusion. This suggests that sub-micron particles could deposit within diseased vascular districts more efficiently than conventional nanoparticles
Multiscale Simulation as a Framework for the Enhanced Design of Nanodiamond-Polyethylenimine-Based Gene Delivery
Nanodiamonds (NDs) are emerging carbon platforms with
promise as
gene/drug delivery vectors for cancer therapy. Specifically, NDs functionalized
with the polymer polyethylenimine (PEI) can transfect small interfering
RNAs (siRNA) in vitro with high efficiency and low cytotoxicity. Here
we present a modeling framework to accurately guide the design of
ND-PEI gene platforms and elucidate binding mechanisms between ND,
PEI, and siRNA. This is among the first ND simulations to comprehensively
account for ND size, charge distribution, surface functionalization,
and graphitization. The simulation results are compared with our experimental
results both for PEI loading onto NDs and for siRNA (c-Myc) loading
onto ND-PEI for various mixing ratios. Remarkably, the model is able
to predict loading trends and saturation limits for PEI and siRNA
while confirming the essential role of ND surface functionalization
in mediating ND-PEI interactions. These results demonstrate that this
robust framework can be a powerful tool in ND platform development,
with the capacity to realistically treat other nanoparticle systems