| Tumor-microenvironment-responsive nanozymes showed potential applications in magnetic resonance imaging(MRI)and photodynamic therapy(PDT).Overcoming tumor hypoxia and realizing“off-on”modulation of MRI/PDT were very significant for developing intelligent and enhanced nanozymes with visualized theranostics.In this dissertation,gold nanoclusters(AuNCs)as the basic unit,by coating mesoporous silicon(mSiO2)and manganese dioxide(MnO2),hydrogen peroxide(H2O2)-responsive nanozyme(AuNCs@mSiO2@MnO2)was constructed,and the"off-on"modulation and enhancement of MRI/PDT were realized.The main research results were obtained as follows:(1)H2O2-responsive AuNCs@mSiO2@MnO2nanozyme was constructed to realize the“off-on”modulation and enhancement of MRI and singlet oxygen(1O2)generation.The results showed that the average size of AuNCs@mSiO2@MnO2was about 150 nm,and the AuNCs were uniformly embedded into mSiO2channels.In neutral physiological environment(pH=7.4),the stable coating of MnO2turned off MRI/1O2,the 1O2yield and T1-weighted MR relaxation were only 0%and 9.70 m M-1s-1.However,in acidic environment(pH=6.5),MnO2reacted with endogenous H2O2to produce O2,and itself was degraded into Mn2+,the 1O2yield and T1-weighted MR relaxation increased to 74.18%and 25.31 m M-1s-1,achieving MRI/1O2turning on and enhancement.(2)MDA-MB-435 breast cancer tumor-bearing nude mice were established,and the enhanced MRI/PDT performances were realized by H2O2-responsive AuNCs@mSiO2@MnO2nanozymes.The results showed that AuNCs@mSiO2@MnO2had good in vitro/in vivo biocompatibility,H2O2-responsive intracellular 1O2generation and in vitro/in vivo MRI performance.Under the irradiation of 635 nm laser,the viability of MDA-MB-435 cells was decreased to 8.24%.Moreover,the tumor completely disappeared and the survival rate was100%within 50 days,showing safe and high-efficient in vitro/in vivo PDT performance. |
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