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(...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.展开更多
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)+6 种基金China Postdoctoral Science Foundation(2019M650259)the Youth Innovation Team of Shaanxi UniversitiesNatural 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)。
文摘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.
