Hypoxia severely impedes the therapeutic efficacies of tumor chemotherapy, radiotherapy and conventional photodynamic therapy(type Ⅱ PDT). Herein, we proposed a nonplanar near-infrared(NIR)-absorbing hyperthermia and...Hypoxia severely impedes the therapeutic efficacies of tumor chemotherapy, radiotherapy and conventional photodynamic therapy(type Ⅱ PDT). Herein, we proposed a nonplanar near-infrared(NIR)-absorbing hyperthermia and superoxide radical(O^(-)_(2)) photogenerator(TB) against hypoxic tumors. TB particularly possessed a favorable O^(-)_(2) generation capability under 808 nm laser irradiation with the donoracceptor-donor(D-A-D) molecular structure. Moreover, owing to molecular rotation, potent hyperthermia was realized under continuous laser irradiation. For the usage of hypoxic tumor treatment, TB was encapsulated by a block copolymer,poly(ethylene glycol)-b-poly(latic acid)(PEG_(45)-b-PLA_(24)), to fabricate phototheranostic nanoparticles(TB NPs). Due to the twisted molecular structure and the shielding effect of long alkyl chains, the π-π stacking-induced quenching of O^(-)_(2) could be reduced after the fabrication of nano-assemblies. Significantly, TB NPs exhibited satisfactory O^(-)_(2) generation for type I PDT and a simultaneously distinct photothermal conversion efficiency(PCE, 62%) for photothermal therapy(PTT)to combat hypoxic tumor cells. Moreover, the high PCE endowed TB NPs with high-performance photoacoustic(PA)and photothermal imaging capability. In vivo experiments demonstrated that TB NPs possessed an outstanding phototherapeutic efficacy for eradicating hypoxic tumors. This study established a novel approach for constructing oxygenindependent phototherapeutic reagent against hypoxic tumors.展开更多
基金supported by the National Institutes of Health of the US(DP5OD017898 and R01EB017270)the National Science Foundation of the US(1555220)+1 种基金the National Natural Science Foundation of China(32071384)the National Key Research and Development Program of China(2021YFC2102300)。
基金supported by the National Natural Science Foundation of China (21875063 and 21871006)the Science and Technology Commission of Shanghai Municipality for Shanghai International Cooperation Program (19440710600)the Open Funding Project of the State Key Laboratory of Bioreactor Engineering。
文摘Hypoxia severely impedes the therapeutic efficacies of tumor chemotherapy, radiotherapy and conventional photodynamic therapy(type Ⅱ PDT). Herein, we proposed a nonplanar near-infrared(NIR)-absorbing hyperthermia and superoxide radical(O^(-)_(2)) photogenerator(TB) against hypoxic tumors. TB particularly possessed a favorable O^(-)_(2) generation capability under 808 nm laser irradiation with the donoracceptor-donor(D-A-D) molecular structure. Moreover, owing to molecular rotation, potent hyperthermia was realized under continuous laser irradiation. For the usage of hypoxic tumor treatment, TB was encapsulated by a block copolymer,poly(ethylene glycol)-b-poly(latic acid)(PEG_(45)-b-PLA_(24)), to fabricate phototheranostic nanoparticles(TB NPs). Due to the twisted molecular structure and the shielding effect of long alkyl chains, the π-π stacking-induced quenching of O^(-)_(2) could be reduced after the fabrication of nano-assemblies. Significantly, TB NPs exhibited satisfactory O^(-)_(2) generation for type I PDT and a simultaneously distinct photothermal conversion efficiency(PCE, 62%) for photothermal therapy(PTT)to combat hypoxic tumor cells. Moreover, the high PCE endowed TB NPs with high-performance photoacoustic(PA)and photothermal imaging capability. In vivo experiments demonstrated that TB NPs possessed an outstanding phototherapeutic efficacy for eradicating hypoxic tumors. This study established a novel approach for constructing oxygenindependent phototherapeutic reagent against hypoxic tumors.
