Tumor Microenvironment Activated Degradable Multifunctional Nanoreactor for Synergistic Cancer Therapy and Glucose SERS Feedback

Summary Integration of disease diagnosis and therapy in vivo by nanotechnology is a challenge in the design of multifunctional nanocarriers. Herein, we report an intelligent and degradable nanoreactor, an assembly of the 4-mercaptobenzonitrile decorated silver nanoparticles (AgNPs@MBN) and the glucose oxidase (GOx) loaded metal-organic-framework (ZIF-8@GOx), which can be activated by tumor microenvironment to start the catalytic cascade-enhanced chemo-starvation synergistic therapy and simultaneous self-sense of cellular glucose level. Under the mild acidic microenvironment of tumor, the nanoreactor will collapse to release GOx that triggers a catalytic cascade reaction in vivo, depleting glucose, etching AgNPs@MBN, and producing toxic H2O2, Ag+, and Zn2+ ions, and all of which work together to inhibit tumor growth. The AgNPs@MBN as SERS nanoprobe reads out glucose concentration noninvasively in tumor to achieve instant feedback of therapeutic progression. This work proposes a promising example of using enzyme-encapsulated biomineralized MOFs as an effective anticarcinogen for clinical applications.