Pharmacotherapy
of vascular anomalies has limited efficacy and
potentially limiting toxicity. Targeted nanoparticle (NP) drug delivery
systems have the potential to accumulate within tissues where the
vasculature is impaired, potentially leading to high drug levels (increased
efficacy) in the diseased tissue and less in off-target sites (less
toxicity). Here, we investigate whether NPs can be used to enhance
drug delivery to bioengineered human vascular networks (hVNs) that
are a model of human vascular anomalies. We demonstrate that intravenously
injected phototargeted NPs enhanced accumulation of NPs and the drug
within hVNs. With phototargeting we demonstrate 17 times more NP accumulation
within hVNs than was detected in hVNs without phototargeting. With
phototargeting there was 10-fold more NP accumulation within hVNs
than in any other organ. Phototargeting resulted in a 6-fold increase
in drug accumulation (doxorubicin) within hVNs in comparison to animals
injected with the free drug. Nanoparticulate approaches have the potential
to markedly improve drug delivery to vascular anomalies.
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