Interaction of nanoparticles with pulsed light and ultrasound for therapy and drug delivery

We proposed to use interaction of nanoparticles with light or ultrasound that produces direct thermal or mechanical damage to tumors or enhances delivery of anti-cancer macromolecular drugs and genes in tumors. Limited... [ view full abstract ]

We proposed to use interaction of nanoparticles with light or ultrasound that produces direct thermal or mechanical damage to tumors or enhances delivery of anti-cancer macromolecular drugs and genes in tumors. Limited penetration of anti-cancer drugs and genes in tumors substantially reduces efficacy and safety of cancer chemo- and biotherapy.  Interaction of light or ultrasound with strongly-absorbing or porous nanoparticles, respectively, may enhance drug and gene delivery or produce damage to tumors without drugs.  The nanoparticles incorporating metal (gold, silver, etc.), carbon, or dye that strongly absorb light as well as porous, biodegradable nanoparticles can selectively accumulate in tumor blood vessels using passive delivery based on enhanced permeability and retention (EPR) effect or active delivery using targeting molecules. Our experimental studies were performed with optically- and ultrasound- active nanoparticles in vitro in tumors and in vivo in mice with human breast, colon, and prostate tumors. Strongly-absorbing nanoparticles and biodegradable polymer PLGA (150 – 200 nm sized) were used for optical and ultrasound therapy, respectively. We studied kinetics of the nanoparticles injected in the tail vein of mice bearing human tumors by using high-resolution ultrasound imaging systems (resolution up to 30 microns). Precise, sub-mm damage to tumors was produced by the interaction of the nanoparticles with focused ultrasound. Tumor thermotherapy was performed using interaction of near infra-red laser pulses with the nanoparticles and demonstrated severe damage to the tumors. Moreover, we developed and built an optoacoustic system for monitoring kinetics of the nanoparticles in the tumors in vivo and monitoring of the tumor thermotherapy in real time. Our results demonstrated that the interaction of nanoparticles with pulsed light or ultrasound produce thermal or mechanical damage to tumors and enhances delivery of anti-cancer drugs and genes in tumors.