The design of enzyme mimics from stable and nonprotein systems is especially attractive for applications in highly specific cancer diagnosis and treatment, and it has become an emerging field in recent years. Herein, metal crosslinked polymeric nanogels (MPGs) were prepared using FeII ion coordinated biocompatible acryloyl‐lysine polymer brushes obtained from an enzyme‐catalyzed atomic transfer radical polymerization (ATRPase) method. The monoatomic and highly dispersed Fe ions in the MPGs serve as efficient crosslinkers of the gel network, and also as active centers of multienzyme mimics of superoxide dismutase (SOD) and peroxidase (POD). The catalytic activities were compared to those of conventional Fe‐based nanozymes. Studies on both cells and animals verify that efficient reactive oxygen species (ROS) responsive biofluorescence imaging can be successfully realized using the MPGs.

The design of enzyme mimics from stable and nonprotein systems is especially attractive for applications in highly specific cancer diagnosis and treatment, and it has become an emerging field in recent years. Herein, metal crosslinked polymeric nanogels (MPGs) were prepared using FeII ion coordinated biocompatible acryloyl‐lysine polymer brushes obtained from an enzyme‐catalyzed atomic transfer radical polymerization (ATRPase) method. The monoatomic and highly dispersed Fe ions in the MPGs serve as efficient crosslinkers of the gel network, and also as active centers of multienzyme mimics of superoxide dismutase (SOD) and peroxidase (POD). The catalytic activities were compared to those of conventional Fe‐based nanozymes. Studies on both cells and animals verify that efficient reactive oxygen species (ROS) responsive biofluorescence imaging can be successfully realized using the MPGs.

Many tumor therapies take advantage of upsetting the redox balance in tumor cells, but to do so requires excessive biochemical or physical attacks. The high‐throughput simulation using multi‐pathway techniques described herein can yield an increased efficacy in bio‐oxidation. In this study, compartmental hierarchical nanoreactors are developed as an efficient multi‐pathway singlet oxygen (1O2) generation system for superactive biocatalytic tumor therapy. The penetrated super cavity and connected dual‐mesopore channels of the compartmental multienzyme nanoreactors are designed using the proposed heterogeneous template assembly for multi‐enzyme complex (superoxide dismutase (SOD)‐lactoperoxidase (LPO)) and photosensitizer molecule (indocyanine green (ICG)) encapsulation. Benefiting by the enhanced direct substrate diffusion between the interacting SOD–LPO complex and decrease in external diffusion, the parallel catalysis combined by the superactive cascade biocatalysis and enzyme‐promoted photosensitization effect is verified by this compartmental silica nanoreactor system. The parallel pathways not only make full use of the products of SOD (H2O2 and O2), but also exhibit outstanding capability for 1O2 production, at ≈2.15 and 1.70 times augmented 1O2, respectively. Both in vitro and in vivo studies demonstrate the synergetic 1O2‐mediated inhibition of tumor proliferation, lending this strategy great potential for the treatment of hypoxic tumors.

The self-assembled phospholipid-or cytosolassociated multienzyme complexes constitute necessary components of the foundation of life. As a proof of concept, metalcoordinated supramolecular nanogels (MCSGs) have been designed, with the self-assembly of di-lysine coordinated iron (Fe(Lys) 2 )-functionalized peptide gelators on the interface by an in situ amidation-induced protonation process. The monoatomic and highly dispersed active centers of Fe(Lys) 2 offered the nanogel mimics with excellent reaction rates due to the high density and nano compartmental structure similar to the natural matrix-associated multienzyme complex. SiO 2 @ MCSGs show both superoxide dismutase (SOD) activity and peroxidase (POD) activity, and the higher activities compared with the activity of free Fe(Lys) 2 molecules can be detected. After loading the substrate 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS), SiO 2 @MCSGs ABTS can responsively convert O 2 − • in the tumor microenvironment into H 2 O 2 intermediates and then tandem catalyzed the oxidization of ABTS for contrast photoacoustic (PA) imaging of tumor by the SOD-POD mimic activity, showing their great potential as the efficient enzymatic agents for pathological theranostics.

No abstract