首页|NIR-Ⅱ imaging-guided precise photodynamic therapy for augmenting tumor-starvation therapy by glucose metabolism reprogramming interference
NIR-Ⅱ imaging-guided precise photodynamic therapy for augmenting tumor-starvation therapy by glucose metabolism reprogramming interference
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Metabolic reprogramming is a mechanism by which cancer cells alter their metabolic patterns to pro-mote cell proliferation and growth,thereby enabling their resistance to external stress.2-Deoxy-D-glucose(2DG)can eliminate their energy source by inhibiting glucose glycolysis,leading to cancer cell death through starvation.However,a compensatory increase in mitochondrial metabolism inhibits its efficacy.Herein,we propose a synergistic approach that combines photodynamic therapy(PDT)with starvation therapy to address this challenge.To monitor the nanodrugs and determine the optimal trig-gering time for precise tumor therapy,a multifunctional nano-platform comprising lanthanide-doped nanoparticle(LnNP)cores was constructed and combined with mesoporous silicon shells loaded with 2DG and photosensitizer chlorin e6(Ce6)in the mesopore channels.Under 980 nm near-infrared light excitation,the downshifted 1550 nm fluorescence signal in the second near-infrared(NIR-Ⅱ,1000-1700 nm)window from the LnNPs was used to monitor the accumulation of nanomaterials in tumors.Furthermore,upconverted 650 nm light excited the Ce6 to generate singlet oxygen for PDT,which dam-aged mitochondrial function and enhanced the efficacy of 2DG by inhibiting hexokinase 2 and lactate dehydrogenase A expressions.As a result,glucose metabolism reprogramming was inhibited and the effi-ciency of starvation therapy was significantly enhanced.Overall,the proposed NIR-Ⅱ bioimaging-guided PDT-augmented starvation therapy,which simultaneously inhibited glycolysis and mitochondria,facili-tated the effects of a cancer theranostic system.
Nanomedicine and Intestinal Microecology Research Center,Shanghai Tenth People's Hospital,School of Medicine,Tongji University,Shanghai 200072,China
Department of Chemistry,Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials,State Key Laboratory of Molecular Engineering of Polymers and iChem,Fudan University,Shanghai 200433,China
State Key Laboratory of High Performance Ceramics and Superfine Microstructure,Shanghai Institute of Ceramics Chinese Academy of Sciences,Shanghai 200050,China
国家自然科学基金国家自然科学基金国家自然科学基金Basic Research Program of Shanghai Municipal GovernmentNatural Science Foundation of Shanghai Municipal Government中国博士后科学基金Shanghai Postdoctoral Excellence Program
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