Polymeric nanocarriers for specific drug delivery in the cellular environment

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Researchers of University of Soochow, China, have described the co-encapsulation of a phototermal dye (cypate) and a drug (paclitaxel) in a polymeric nanoassemblies (PEG-a-PCL-SS-P(NIPAM-co-DMA) star quaterpolymer) for dual cancer therapy (Fig. A). Thanks to the polymer design, high payload was observed (20% of each active units). To control the release of the paclitaxel, the polymer contains a pH (acetal group) and reductive (disulfide) sensitive function. Thus, the authors want to take advantage of the cellular environment to control the delivery of paclitaxel i.e. the lysosomal acidic medium and the gluthatione reducing agent in the cytoplasme. The dye mediates under near infra-red irradiation the heat generation to facilitate the nanocarriers dissolution (LCST of the nano-assembly equal to 44.7°C). Results in solution show clearly that primordial effect in the drug release of temperature is facilitated by the action of pH and reducing species (Fig. B). Moreover, acidic condition amplified the heat generation of the dye. In vitro experiments demonstrated the uptake by clathrin-mediated mechanism of the nanocarriers and the lysosomal disruption under illumination. This disruption allows the paclitaxel translocation. However, in vivo the nanocarriers keep intact after injection as demonstrated by the preferential and colocalisation of drug and dye in the tumor (Fig. C). From a therapeutics point of view, only the combination of paclitaxel delivery and heat generation permit the stop the tumoral growth (Fig. D).

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A/ Description of the nanocarriers; B/ Release of paclitaxel in solution with the action of different stimuli; C/ Biodistribution of paclitaxel (several nanocarriers and references); D/ Evolution of relative tumor volume, function of time.