In vivo assembly of nanoparticle components to improve targeted cancer imaging.
Many small molecular anticancer agents are often ineffective at detecting or treating cancer due to their poor pharmacokinetics. Using nanoparticles as carriers can improve this because their large size reduces clearance and improves retention within tumors, but it also slows their rate of transfer from circulation into the tumor interstitium. Here, we demonstrate an alternative strategy whereby a molecular contrast agent and engineered nanoparticle undergo in vivo molecular assembly within tumors, combining the rapid influx of the smaller and high retention of the larger component. This strategy provided rapid tumor accumulation of a fluorescent contrast agent, 16- and 8-fold faster than fluorescently labeled macromolecule or nanoparticle controls achieved. Diagnostic sensitivity was 3.0 times that of a passively targeting nanoparticle, and this improvement was achieved 3 h after injection. The advantage of the in vivo assembly approach for targeting is rapid accumulation of small molecular agents in tumors, shorter circulation time requirements, possible systemic clearance while maintaining imaging sensitivity in the tumor, and nanoparticle anchors in tumors can be utilized to alter the pharmacokinetics of contrast agents, therapeutics, and other nanoparticles. This study demonstrates molecular assembly of nanoparticles within tumors, and provides a new basis for the future design of nanomaterials for medical applications.
Institute of Biomaterials and Biomedical Engineering, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, Canada M5S 3E1.
Steven D
SD
Perrault
Warren C W
WC
Chan
D000818:Animals; D019921:Biotinylation; D002138:Calibration; D003287:Contrast Media / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods*; D004058:Diffusion; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D009369:Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy*; D011092:Polyethylene Glycols / Q000737:chemistry
D003287:Contrast Media; D005456:Fluorescent Dyes; D011092:Polyethylene Glycols