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
The nucleotide sequence deduced from the amino acid sequence of the scorpion insectotoxin AaIT was chemically synthesized and was expressed in Escherichia coli. The authenticity of this in vitro expressed peptide was ...The nucleotide sequence deduced from the amino acid sequence of the scorpion insectotoxin AaIT was chemically synthesized and was expressed in Escherichia coli. The authenticity of this in vitro expressed peptide was confirmed by N-terminal peptide sequencing. Two groups of bioassays, artificial diet incorporation assay and contact insecticidal effect assay, were carried out separately to verify the toxicity of this recombinant toxin. At the end of a 24 h experimental period, more than 60% of the testing diamondback moth (Plutella xylostella) larvae were killed in both groups with LC50 value of 18.4 microM and 0.70 microM respectively. Cytotoxicity assay using cultured Sf9 insect cells and MCF-7 human cells demonstrated that the toxin AaIT had specific toxicity against insect cells but not human cells. Only 0.13 microM recombinant toxin was needed to kill 50% of cultured insect cells while as much as 1.3 microM toxin had absolutely no effect on human cells. Insect cells produced obvious intrusions from their plasma membrane before broken up. We infer that toxin AaIT bind to a putative sodium channel in these insect cells and open the channel persistently, which would result in Na+ influx and finally cause destruction of insect cells.展开更多
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.
文摘钙激活氯通道(calcium-activated chloride channels,CaCCs)组织分布广泛,参与了众多生理过程,如感觉传导、神经和心肌兴奋性调节、腺体和上皮分泌等,甚至可能参与细胞分裂周期与细胞增殖。钙激活氯通道生理病理意义如此重要,但直到2008年才报道了跨膜蛋白16A(transmem-brane protein 16A,TMEM16A)为钙激活氯通道的分子基础,同时研究揭示TMEM16A在一些肿瘤组织中表达明显上调。该文即对钙激活氯通道的生理、病理学意义进行综述。
基金This work was supported by a grant from 863High Technology Program,Chinese Ministry of Sci-ence and Technology
文摘The nucleotide sequence deduced from the amino acid sequence of the scorpion insectotoxin AaIT was chemically synthesized and was expressed in Escherichia coli. The authenticity of this in vitro expressed peptide was confirmed by N-terminal peptide sequencing. Two groups of bioassays, artificial diet incorporation assay and contact insecticidal effect assay, were carried out separately to verify the toxicity of this recombinant toxin. At the end of a 24 h experimental period, more than 60% of the testing diamondback moth (Plutella xylostella) larvae were killed in both groups with LC50 value of 18.4 microM and 0.70 microM respectively. Cytotoxicity assay using cultured Sf9 insect cells and MCF-7 human cells demonstrated that the toxin AaIT had specific toxicity against insect cells but not human cells. Only 0.13 microM recombinant toxin was needed to kill 50% of cultured insect cells while as much as 1.3 microM toxin had absolutely no effect on human cells. Insect cells produced obvious intrusions from their plasma membrane before broken up. We infer that toxin AaIT bind to a putative sodium channel in these insect cells and open the channel persistently, which would result in Na+ influx and finally cause destruction of insect cells.
