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The currently low delivery efficiency and limited tumor penetration of nanoparticles remain two major challenges of cancer nanomedicine. The group lead byProf. Wang Jun (USTC) and Prof. NIE Shuming (Georgia Tech and Emory), developed clustered nano-superstructures with tumor microenvironment sensitivity, to facilitate penetration of nanoparticles into deep tumor tissues by transforming the particle size. Our newest work published in ACS Nano (DOI: 10.1021/acsnano.6b02326), reported a class of pH-responsive nanoparticle superstructures with ultrasensitive size switching in the acidic tumor microenvironment for improved tumor penetration and effective in vivo drug delivery. The superstructures were constructed from amphiphilic polymer directed assembly of platinum-prodrug conjugated polyamidoamine (PAMAM) dendrimers, in which the amphiphilic polymer contained ionizable tertiary amine groups for rapid pH-responsiveness. These superstructures had an initial size of ~80 nm at neutral pH (e.g. in blood circulation), but once deposited in the slightly acidic tumor microenvironment (pH ~6.5-7.0), they underwent a dramatic and sharp size transition within a very narrow range of acidity (less than 0.1-0.2 pH units), and dissociated instantaneously into the dendrimer building blocks (less than 10 nm in diameter). This rapid size-switching feature not only facilitated nanoparticle extravasation and accumulation via the enhanced permeability and retention (EPR) effect, but also allowed faster nanoparticle diffusion and more efficient tumor penetration.This work was financially supported by the National Basic Research Program of China, National Natural Science Foundation of China.
