  Mesoporous silica nanoparticles have been reported as suitable drug carriers,
but their successful delivery to target tissues following systemic
administration remains a challenge. In the present work, ultrasound-induced
inertial cavitation was evaluated as a mechanism to promote their extravasation
in a flow-through tissue-mimicking agarose phantom. Two different ultrasound
frequencies, 0.5 or 1.6 MHz, with pressures in the range 0.5-4 MPa were used to
drive cavitation activity which was detected in real time. The optimal
ultrasound conditions identified were employed to deliver dye-loaded
nanoparticles as a model for drug-loaded nanocarriers, with the level of
extravasation evaluated by fluorescence microscopy. The same nanoparticles were
then co-injected with submicrometric polymeric cavitation nuclei as a means to
promote cavitation activity and decrease the required in-situ acoustic pressure
required to attain extravasation. The overall cavitation energy and penetration
of the combination was compared to mesoporous silica nanoparticles alone. The
results of the present work suggest that combining mesoporous silica
nanocarriers and submcrometric cavitation nuclei may help enhance the
extravasation of the nanocarrier, thus enabling subsequent sustained drug
release to happen from those particles already embedded in the tumour tissue.
