Mechanism of laser-induced drug delivery in tumors

Penetration of anti-cancer drugs (especially macromolecular agents) from blood in tumor cells is limited due to the presence of physiological barriers: tumor capillary wall, slow diffusion in the interstitium, and cancer cell membrane. Interaction of exogenous nano- or microparticles with laser or ultrasonic radiation may enhance drug delivery in tumor cells due to laser- or ultrasound-induced cavitation. Our previous studies demonstrated enhanced delivery of model macromolecular anti-cancer drugs in tissues in vitro when laser or ultrasonic radiation is applied. In this paper, we studied laser-induced cavitation in suspension of strongly absorbing particles and laser-enhanced drug delivery in human colon tumors of nude mice in vivo. Cavitation kinetics and thresholds were measured for carbon and colored polystyrene particle suspensions. Histological examination of control and irradiated tumors with fluorescent microscopy demonstrated that Q-switched Nd:YAG laser irradiation enhances delivery of a model macromolecular drug (FITC-dextran) in tumor blood vessel and interstitium. Enhanced delivery of an anti-cancer drug (5-FU) that is currently used in clinics resulted in tumor necrosis and inhibited tumor growth. Results of our studies suggest that the drug delivery enhancement is due to cavitation produced by local heating of particles with pulsed laser radiation.