A systems approach to engineering cancer nanotechnologies

[摘要] (cont.) In the second section of this thesis, indirect mechanisms of nanoparticle interaction-where nanoparticles communicate at a distance via intermediates-are engineered to amplify nanoparticle targeting to regions of tumor invasion in vivo. Two nanosystems are synthesized wherein intravenously administered nanoparticles that have successfully targeted tumors broadcast the tumor;;s location to other nanoparticles in circulation to recruit their amplified local accumulation. In mice, one of these systems intravenously delivers >40-fold higher drug doses to tumors than non-communicating controls, leading to durable repression of tumor growth and significantly improved host survival. Together, these systems highlight the potential for interactive nanoparticle systems to perform highly complex functions in vivo. In contrast to the current strategy of injecting large populations of nanoparticles that carry out identical, often competitive functions in vivo, this work promotes a paradigm of ;;systems nanotechnology,;; directed toward the construction of nanoparticle systems that produce emergent behaviors for enhancing in vivo diagnostics, regenerative medicines, and therapeutics.

[发布机构] Massachusetts Institute of Technology