Nanoparticles and ultrasound for delivery of model macromolecular anti-cancer drugs in tumors

Penetration of macromolecular anti-cancer agents from blood into tumor cells is poor due to the physiological barriers: tumor capillary wall, interstitium, and cancer cell membrane. We proposed to use laser- or ultrasound-induced cavitation to enhance anti-cancer drug delivery through these barriers. Interaction of ultrasound with exogenous nanoparticles with certain acoustic properties may provide cavitation selectively in tumors and, therefore, may provide safe and efficient delivery of anti-cancer drugs in cancer cells without damage to normal tissues. In this paper, we studied enhanced delivery of model macromolecular anti-cancer drugs with ultrasound-induced cavitation in mice bearing human colon (KM20) and breast (MCF-7) tumors. Fluorescent rhodamine-dextrans of different molecular weight (10, 70, and 2,000 kDa) served as model drugs simulating antisense oligonucleotides, antibodies, and genes, respectively. Immunohistochemical staining of tumor vasculature with CD31 was used to visualize tumor blood vessels. Our studies demonstrated enhanced penetration of the drugs from blood vessels into tumor interstitium when ultrasound was applied in combination with polymer nanoparticle injections. Our results suggest that this drug delivery technique can potentially be used for efficient cancer chemo- and biotherapy.