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Heavy-atom engineered hypoxia-responsive probes for precisive photoacoustic imaging and cancer therapy
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作者 Ling-Ling Wu Xiangchuan Meng +5 位作者 Qingyang Zhang Xiaowan Han Feiya Yang Qinghua Wang Hai-Yu Hu Nianzeng Xing 《Chinese Chemical Letters》 SCIE CAS CSCD 2024年第4期316-320,共5页
Photoacoustic agents combining photodynamic therapy(PDT) and photothermal therapy(PTT) functions have emerged as potent theranostic agents for combating cancer. The molecular approaches for enhancing the near-infrared... Photoacoustic agents combining photodynamic therapy(PDT) and photothermal therapy(PTT) functions have emerged as potent theranostic agents for combating cancer. The molecular approaches for enhancing the near-infrared(NIR)-absorption and maximizing non-radiative energy transfer are essential for effective photoacoustic imaging(PAI) and therapy applications. In addition, such molecules with high specificity and affinity to cancer cells are urgently needed, which would further decrease the side effect during treatments. In this study, we applied a heavy-atom engineering strategy and introduced p-aminophenol,-thio, and-seleno moieties into NIR heptamethine cyanine(Cy7) skeleton(Cy7-X-NH_(2), X = O, S, Se) to significantly increase photothermal conversion efficiency for PTT and promote intersystem crossing for PDT.Additionally, we designed a series of nitroreductase(NTR)-activated photoacoustic probes(Cy7-X-NO_(2),X = O, S, Se), and target hypoxic tumors with NTR overexpression. Our prostate cancer targeting probe,Cy7-Se-NO_(2)-KUE, exhibited specific tumor photoacoustic signals and effective tumor killing through outstanding synergistic PTT/PDT in vivo. These findings highlighted a versatile strategy for cancer photoacoustic diagnosis and enhanced phototherapy. 展开更多
关键词 Heavy-atom effect PHOTOTHERAPY Photoacoustic imaging hypoxia-responsive Prostate cancer
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Calixarene-integrated nano-drug delivery system for tumortargeted delivery and tracking of anti-cancer drugsin vivo 被引量:2
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作者 Lina Xu Jingshan Chai +5 位作者 Ying Wang Xinzhi Zhao Dong-Sheng Guo Linqi Shi Zhanzhan Zhang Yang Liu 《Nano Research》 SCIE EI CSCD 2022年第8期7295-7303,共9页
Nano-drug delivery systems(nanoDDS)have been extensively investigated clinically to improve the therapeutic effect of anticancer drugs.However,the complicated synthesis during the preparation as well as the potential ... Nano-drug delivery systems(nanoDDS)have been extensively investigated clinically to improve the therapeutic effect of anticancer drugs.However,the complicated synthesis during the preparation as well as the potential drug leakage during transportation has greatly limited their general application.In this work,a calixarene-integrated nanoDDS(CanD)that achieves tumor-targeted delivery and tracking of anti-cancer drugs in vivo is presented.The hypoxia-responsive calixarene(SAC4A)exhibits high binding affinity to a series of anti-cancer drugs and rhodamine B(RhB)under normoxic condition while decreasing the binding affinity under hypoxic condition,which leads to the drug release and fluorescence recovery simultaneously.Furthermore,the hypoxia-responsiveness of SAC4A conveys CanD with tumor-targeting ability,resulting in the enrichment of the drug in tumors and enhancement in tumor suppression in mice.Moreover,CanD could become a general platform allowing the delivery of a wide scope of anti-cancer drugs that have strong host-guest interaction with SAC4A. 展开更多
关键词 drug delivery system CALIXARENE host-guest interaction hypoxia-responsiveness drug tracking
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The targeting expression of the vascular endothelial growth factor gene in endothelial cells regulated by HRE.ppET-1 被引量:1
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作者 ZHENG XiangRong, ZHANG ShangShang, YANG YuJia, WANG Xia, ZHONG Le & YU XiaoHe Department of Pediatrics, Xiangya Hospital, Central South University, Changsha 410008, China 《Science China(Life Sciences)》 SCIE CAS 2008年第11期959-965,共7页
The success of gene therapy depends largely on the efficacy of gene delivery vector systems that can deliver genes to target organs or cells selectively and efficiently with minimal toxicity. Here, we show that by usi... The success of gene therapy depends largely on the efficacy of gene delivery vector systems that can deliver genes to target organs or cells selectively and efficiently with minimal toxicity. Here, we show that by using the HRE.ppET-1 regulatory element, we were able to restrict expression of the transgene of vascular endothelial growth factor (VEGF) to endothelial cells exclusively in hypoxic conditions. Eukaryotic expression vectors such as pEGFP-HRE.ppET-1, pcDNA3.1-VEGF+Pa, pcDNA3.1-ppET-1+ EGF+Pa, and pcDNA3.1-HRE.ppET-1+VEGF+Pa were constructed by using a series of nuclear molecule handling methods like PCR, enzyme digestion. The recombinant vectors were transfected into HUVEC cells and HL7702 cells by the lipofectin method. GFP expression was observed with a fluorescence microscope to validate the specificity of expression in endothelial cells under the regulation of HRE.ppET-1 element. Cobalt chloride (final concentration 100 μmol/L) was added to the medium to mimic hypoxia in vitro. After transfection of vectors, the expression of VEGF mRNA was detected by RT-PCR, and the expression of VEGF was detected by Western blotting and ELISA methods under normoxia and hypoxia, respectively. The cell proliferation rate was detected by the MTT test. The ex- pression of GFP revealed that the exterior gene was transcripted effectively in endothelial cells regu- lated by the HRE.ppET-1 element, while the expression of GFP was very weak in nonendothelial cells. The results of RT-PCR, Western blotting and ELISA showed that VEGF gene expression in the pcDNA3.1-HRE.ppET-1+VEGF+Pa group and in the pcDNA3.1-ppET-1+VEGF+Pa group was higher in hypoxia than it was in normoxia (P<0.05). The MTT test showed that the proliferation rate of HUVEC transfected with HPVA under hypoxia exceeded that of the control group. We conclude that the HRE.ppET-1 element was expressed specifically in endothelial cells, and can increase the expression of VEGF in hypoxia and stimulate proliferation of endothelial cells. Taking advantage of these facts could greatly improve the efficiency of gene therapy. The vector would be valuable for various gene transfer studies targeting endothelial cells. 展开更多
关键词 hypoxia-responsive element human preproendothelin-1 PROMOTER vascular ENDOTHELIAL growth factor ENDOTHELIAL cells
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