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A nano‐complex system to overcome antagonistic photo‐chemo combination cancer therapy

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Abstract Photo‐Chemo combination therapy has been intensively investigated for treatment of cancers, especially multidrug resistance cancer. However, antagonistic interactions between chemo‐drugs and photosensitizers are frequently reported, and drugs doses and… Click to show full abstract

Abstract Photo‐Chemo combination therapy has been intensively investigated for treatment of cancers, especially multidrug resistance cancer. However, antagonistic interactions between chemo‐drugs and photosensitizers are frequently reported, and drugs doses and treatment sequences have been changed to overcome the problems. We observed the antagonistic effect by a decrease in singlet oxygen generation from the photosensitizer when Dox was in close physical proximity. To control the distance between Dox and the photosensitizer, we developed a novel pH‐sensitive poly ionomer complex system composed of PEG‐PLL(‐g‐Ce6) [Chlorin e6 grafted poly(ethylene glycol)‐poly(l‐lysine)] and PEG‐PLL(‐g‐DMA)‐PLA [2,3‐dimethylmaleic anhydride grafted poly(ethylene glycol)‐poly(l‐lysine)‐poly(lactic acid)] and evaluated this system with regard to singlet oxygen generation and antiproliferative activity against MCF‐7/Dox cells. Enhanced singlet oxygen generation and antiproliferative activities were observed in vitro and in vivo for the poly ionomer complex system compared to PEG‐PLL(‐g‐Ce6)‐PLA/Dox due to the change in distance between Dox and Ce6 in the PIC system under acidic conditions. Our results highlight the importance of interactions between co‐loaded drugs in combination therapy, and provide new insights into design principles for tailor‐made nanomedicine platforms. Graphical abstract Figure. No Caption available. HighlightsGeneration and diffusion of singlet oxygens from the Ce6 was decreased when Dox was in close physical proximity to Ce6A poly ionomer complex was developed to keep Ce6 and Dox away from each other under endo‐lysosomal acidic conditionsPIC system enhanced the singlet oxygen generation and antiproliferative activities in vitro and in vivo conditions

Keywords: combination; system; photo chemo; singlet; therapy; complex system

Journal Title: Journal of Controlled Release
Year Published: 2019

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