机构地区:[1]Laboratory of Molecular Imaging and Translational Medicine(MITM),Engineering Research Center of Molecular&Neuroimaging,Ministry of Education,School of Life Science and Technology,Xidian University,Xi’an 710126,China [2]Academy of Advanced Interdisciplinary Research,Xidian University,Xi’an 710071,China [3]Department of Thoracic Surgery,Shanghai Pulmonary Hospital,School of Medicine,Tongji University,Shanghai 200433,China [4]School of Materials Science and Engineering,Tongji University,Shanghai 201804,China [5]School of Chemical and Biomedical Engineering,Nanyang Technological University,Singapore 637457,Singapore
出 处:《Science Bulletin》2022年第3期288-298,共11页科学通报(英文版)
基 金:the National Key Research and Development Program of China(2017YFC1309100,2017YFA0205200,and 2020YFA0211100);National Natural Science Foundation of China(81671753,91959124,21804104,32071406,51922077,and 51872205);China Postdoctoral Science Foundation(2019M650259);the Youth Innovation Team of Shaanxi Universities;Natural Science Foundation of Shaanxi Province of China(2020PT-020);the Fundamental Research Funds for the Central Universities(JB211202,and JC2112);the Open Project Program of the State Key Laboratory of Cancer Biology(Fourth Military Medical University)(CBSKL2019ZDKF06);the Foundation of National Facility for Translational Medicine(Shanghai)(TMSK2020-012);Young Talents Program,and Shanghai Municipal Commission of Health and Family Planning Foundation(2017YQ050)。
摘 要:Dysregulated energy metabolism has recently been recognized as an emerging hallmark of cancer.Tumor cells,which are characterized by abnormal glycolysis,exhibit a lower extracellular pH(6.5–7.0)than nor-mal tissues(7.2–7.4),providing a promising target for tumor-specific imaging and therapy.However,most pH-sensitive materials are unable to distinguish such a subtle pH difference owing to their wide and continuous pH-responsive range.In this study,we developed an efficient strategy for the fabrication of a tumor metabolic acidity-activatable calcium phosphate(CaP)fluorescent probe(termed MACaP9).Unlike traditional CaP-based biomedical nanomaterials,which only work within more acidic organelles,such as endosomes and lysosomes(pH 4.0–6.0),MACaP9 could not only specifically respond to the tumor extra-cellular pH but also rapidly convert pH variations into a distinct fluorescence signal to visually dis-tinguish tumor from normal tissues.The superior sensitivity and specificity of MACaP9 enabled high-contrast visualization of a broad range of tumors,as well as small tumor lesions.虽然肿瘤具有高度异质性,但几乎在所有类型的肿瘤细胞中都普遍存在着代谢异常现象.和正常组织的酸性相比(pH 7.2~7.4),以异常糖酵解为特征的肿瘤细胞具有更低的细胞外酸性(pH 6.5~7.0),为肿瘤的成像和治疗提供了一个潜在靶点.然而绝大多数pH敏感的材料都表现出较宽的pH响应范围,无法区分这种细微的pH差异.在该研究中,研究者通过对探针合成条件的精细调控构建了肿瘤代谢微酸激活的磷酸钙(CaP)荧光探针MACaP9.与传统的CaP纳米探针(通常在更低的pH值条件下(4.0~6.0)才具有响应性能)相比,MACaP9不仅能够被肿瘤微环境的pH特异性激活,而且能够快速地将肿瘤微环境和正常组织之间的细微pH值差异(pH 6.8~7.0、ΔpH=0.2)转变成明显的荧光信号,从而清晰地区分肿瘤和正常组织,显著增加了在体成像时的信噪比.研究结果表明,MACaP9不仅能够对各种类型的肿瘤进行高特异性成像,而且还能够对微小的肿瘤病变进行高灵敏可视化.
关 键 词:Calcium phosphate Activatable probe Cancer imaging Tumor microenvironment Tumor metabolism
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