The depth of light penetration and tumor hypoxia restrict the efficacy of photodynamic therapy(PDT)in triple-negative breast cancer(TNBC),while the overproduction of lactate(LA)facilitates the development,aggressivene...The depth of light penetration and tumor hypoxia restrict the efficacy of photodynamic therapy(PDT)in triple-negative breast cancer(TNBC),while the overproduction of lactate(LA)facilitates the development,aggressiveness,and therapy resistance of TNBC.To address these issues,a self-acting PDT nanosystem(HL@hMnO_(2)-LO_(x)@HA)is fabricated by loading 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha(HPPH),luminol,and LA oxidase(LO_(x))in a hyaluronic acid(HA)-coated hollow manganese dioxide(hMnO_(2))nanoparticle.LO_(x) catalyzes the oxidation of LA into pyruvate and hydrogen peroxide(H_(2)O_(2)),thus depleting the overproduced intratumoral LA.In the acidic tumor microenvironment,H_(2)O_(2) reacts with luminol and hMnO_(2) to yield blue luminescence as well as O_(2) and Mn^(2+),respectively.Mn^(2+)could further enhance this chemiluminescence.HPPH is then excited by the chemiluminescence through chemiluminescence resonance energy transfer for self-illuminated PDT.The generated O_(2) alleviates the hypoxia state of the TNBC tumor to produce sufficient 1O_(2) for self-oxygenation PDT.The Mn^(2+)performs T1 magnetic resonance imaging to trace the self-acting PDT process.This work provides a biocompatible strategy to conquer the limits of light penetration and tumor hypoxia on PDT against TNBC as well as LA overproduction.展开更多
基金the National Key R&D Program of China(2018YFA0704000 and 2020YFA0908800)the National Natural Science Foundation of China(82372116,82071985,and 22104094)+1 种基金the Basic Research Program of Guangdong(2022A1515010620)the Basic Research Program of Shenzhen(JCYJ20200109105620482,JCYJ20220818095806014,and KQTD20190929172538530).
文摘The depth of light penetration and tumor hypoxia restrict the efficacy of photodynamic therapy(PDT)in triple-negative breast cancer(TNBC),while the overproduction of lactate(LA)facilitates the development,aggressiveness,and therapy resistance of TNBC.To address these issues,a self-acting PDT nanosystem(HL@hMnO_(2)-LO_(x)@HA)is fabricated by loading 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha(HPPH),luminol,and LA oxidase(LO_(x))in a hyaluronic acid(HA)-coated hollow manganese dioxide(hMnO_(2))nanoparticle.LO_(x) catalyzes the oxidation of LA into pyruvate and hydrogen peroxide(H_(2)O_(2)),thus depleting the overproduced intratumoral LA.In the acidic tumor microenvironment,H_(2)O_(2) reacts with luminol and hMnO_(2) to yield blue luminescence as well as O_(2) and Mn^(2+),respectively.Mn^(2+)could further enhance this chemiluminescence.HPPH is then excited by the chemiluminescence through chemiluminescence resonance energy transfer for self-illuminated PDT.The generated O_(2) alleviates the hypoxia state of the TNBC tumor to produce sufficient 1O_(2) for self-oxygenation PDT.The Mn^(2+)performs T1 magnetic resonance imaging to trace the self-acting PDT process.This work provides a biocompatible strategy to conquer the limits of light penetration and tumor hypoxia on PDT against TNBC as well as LA overproduction.
