Interaction of radiation with microparticles for enhancement of drug delivery in tumors

Various promising anti-cancer drugs have been proposed for cancer therapy for the past two decades. However, limited success has been achieved in cancer therapy. Slow diffusion of the drugs (especially macromolecular ones with molecular weight greater than 5,000) in the interstitium and their poor penetration through tumor vasculature and cancer cell membrane explain partially this paradox. A novel technique is proposed to alter properties of these barriers and enhance drug delivery in cancer cells with minimal damage to normal tissues. This technique is based on interaction of exogenous nano- and microparticles selectively delivered in tumor blood vessels with radiation resulting in cavitation near the particles. Cavitation may perforate tumor blood vessels and cancer cell membranes and induce microconvection in the interstitium. This yields increased penetration of anti-cancer drugs from blood into cancer cells. Preliminary experiments were performed with various tissues (liver, muscle, kidney, lung) to demonstrate penetration and migration of particles and macromolecules in the interstitium upon irradiation by laser pulses or ultrasound. Q-switched Nd:YAG and Alexandrite laser pulses and ultrasound with the frequency of 50 kHz were used in these studies. Particle penetration was 30-180 μm upon 10-min irradiation by laser pulses or ultrasound that is comparable to the average distance of 200 μm between tumor capillaries. Considerable enhancement of delivery of FITC-dextran (M.W. = 12,000) simulating macromolecular anti-cancer drugs in these tissues was obtained. Our results suggest that the proposed technique can potentially enhance delivery of anti-cancer drugs in tumors of various organs.