Abstract
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.
基金项目
国家自然科学基金(81972221)
国家自然科学基金(32271384)
国家自然科学基金(82271997)
Basic Research Program of Shanghai Municipal Government(20JC1411702)
Natural Science Foundation of Shanghai Municipal Government(20ZR1456100)
中国博士后科学基金(2021M702484)
Shanghai Postdoctoral Excellence Program(2020382)
NETL
NSTL
万方数据