Encapsulating a Single Nanoprobe in a Multifunctional Nanogel for High-Fidelity Imaging of Caspase Activity in Vivo

The formation of a protein corona on nanoprobes in the blood can not only reduce the delivery efficiency to their destination but also inhibit the functions of the nanoprobes. Herein, we report a multifunctional nanogel that can shield a single gold nanoparticle (AuNP) probe from interaction with the serum proteins, virtually eliminating protein corona formation on the nanoprobes. As a result, the delivery efficiency of the nanogel-encapsulated nanoprobes to tumors was dramatically enhanced. When the probes are delivered into target cells, the nanogel shells are degraded in acidic endosomes, where a proton sponge effect occurs instantaneously to release the AuNP probes into the cytoplasm to realize their bioimaging functions. We demonstrated the applicability of these probes for high-fidelity, noninvasive imaging of caspase activity in both cancer cells and in tumors. This strategy offers an exciting opportunity to design high-efficacy nanoprobes for in vivo imaging.