Acute myeloid leukemia(AML)remains a significant concern in modern medicine.Early diagnosis is the key to improving the therapeutic effects of AML.In the present work,a cascade-targeted and activatable NIR-Ⅱ nanoprob...Acute myeloid leukemia(AML)remains a significant concern in modern medicine.Early diagnosis is the key to improving the therapeutic effects of AML.In the present work,a cascade-targeted and activatable NIR-Ⅱ nanoprobe(Ald&A1094@Ag_(2)S)was developed for early detection of AML in an orthotopic model.Upon intravenous injection,Ald&A1094@Ag_(2)S effectively accumulated in bone tissue due to its high affinity for alendronate(Ald)to the bone.Thereafter,the AML microenvironment allowed for the membrane-penetrating peptide TAT(cell‐penetrating peptide(CGRRRQRRKKRG))to be exposed via pH-sensitive hydrazone bond-mediated detaching of bone-targeted ligands,resulting in efficient internalization of nanoprobes in HL60 cells.Endogenous peroxynitrite(ONOO–)in HL60 cells further activated NIR-Ⅱ fluorescence of Ag_(2)S QDs via A1094 oxidation,thereby inhibiting fluorescence resonance energy transfer(FRET).Such a unique cascade-targeted and activatable strategy enables the nanoprobes to only light up the AML lesion region in the bone marrow with negligible background effects,which holds great potential for clinical applications in the future.展开更多
基金supported by the National Key Research and Development Program of China(grant nos.2016YFA0101503 and 2017YFA0205503)the National Natural Science Foundation of China(grant nos.21934007,21778070,and 21671198)+2 种基金Chinese Academy of Sciences(grant nos.XDB32030200,121E32KYSB20180021,and ZDBS-LY-SLH021)the Natural Science Foundation of Jiangsu Province(grant no.BK20170066)Youth Innovation Promotion Association of Chinese Academy of Sciences。
文摘Acute myeloid leukemia(AML)remains a significant concern in modern medicine.Early diagnosis is the key to improving the therapeutic effects of AML.In the present work,a cascade-targeted and activatable NIR-Ⅱ nanoprobe(Ald&A1094@Ag_(2)S)was developed for early detection of AML in an orthotopic model.Upon intravenous injection,Ald&A1094@Ag_(2)S effectively accumulated in bone tissue due to its high affinity for alendronate(Ald)to the bone.Thereafter,the AML microenvironment allowed for the membrane-penetrating peptide TAT(cell‐penetrating peptide(CGRRRQRRKKRG))to be exposed via pH-sensitive hydrazone bond-mediated detaching of bone-targeted ligands,resulting in efficient internalization of nanoprobes in HL60 cells.Endogenous peroxynitrite(ONOO–)in HL60 cells further activated NIR-Ⅱ fluorescence of Ag_(2)S QDs via A1094 oxidation,thereby inhibiting fluorescence resonance energy transfer(FRET).Such a unique cascade-targeted and activatable strategy enables the nanoprobes to only light up the AML lesion region in the bone marrow with negligible background effects,which holds great potential for clinical applications in the future.
