Multifunctioning pH‐responsive nanoparticles from hierarchical self‐assembly of polymer brush for cancer drug delivery

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Abstract
Polymer nanoparticles are extensively explored as drug carriers but they generally have issues of premature burst drug release, slow cellular uptake, and retention in acidic intracellular compartments. Herein, we report multifunctioning three‐layered nanoparticles (3LNPs) that can overcome these problems. The 3LNPs have a poly(ε‐caprolactone) (PCL) core, a pH‐responsive poly[2‐(N,N‐diethylamino)ethyl methacrylate](PDEA) middle layer and a polyethylene glycol (PEG) outer layer. The pH‐responsive PDEA layer is insoluble at pH above 7 but becomes positively charged and soluble via protonation at pH lower than 6.5. Thus, this layer has three functions: it covers on the PCL core inhibiting the premature burst drug release at the physiological pH, becomes positively charged and thus promotes endocytosis for fast cellular internalization in the acidic interstitium of solid tumors, and is highly positively charged in lysosomes to disrupt the lysosomal membrane and release the nanoparticle into the cytosol. The multifunctioning nanoparticles are an efficient carrier for cancer cytosolic drug delivery. © 2008 American Institute of Chemical Engineers AIChE J, 2008

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