Nanozymes, a class of nanomaterials with intrinsic enzyme-like activities, have been widely used as artificial enzymes in biomedical applications. However, how to control their in vivo performance in a target cell is still challenging. Here, we report a novel strategy to coordinate nanozymes to target tumor cells and selectively perform their activity to destruct in vivo tumors. We developed a novel nanozyme using nitrogen-doped porous carbon nanospheres (N-PCNSs) which possess four enzyme-like activities (oxidase, peroxidase, catalase and superoxide dismutase) responsible for reactive oxygen species (ROS) regulation (generation/scavenge). We then introduced ferritin to guide N-PCNSs nanozymes to efficiently transfer into lysosomes and boost ROS generation in a tumor-specific manner, resulting in significant tumor regression in human tumor xenograft mice model. Together, the current study provides first evidence that N-PCNSs are powerful nanozymes with ROS regulatory properties and ferritinylation is a novel strategy to render nanozymes to target tumor in vivo. This work provides a new strategy to coordinate nanozymes for in vivo tumor catalytic therapy. In addition, the intrinsic peroxidase-like activity of graphene quantum dot nanozyme (GQDzyme) effectively converts the 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) into its oxidized form in the presence of H2O2. The oxidized ABTS exhibits strong near-infrared (NIR) absorbance, rendering it to be an ideal contrast agent for PAI. Thus, GQDzyme/ABTS nanoparticle is a novel type of catalytic PAI contrast agent, which is sensitive to H2O2 produced from NPC cells. Furthermore, we develop an approach to construct exosome-like nanozyme vesicle via biomimetic functionalization of GQDzyme/ABTS nanoparticle with natural erythrocyte membrane modified with folate acid. In vivo animal experiments demonstrated that this exosome-like nanozyme vesicle effectively accumulated in NPC and selectively triggered catalytic PAI for NPC. In addition, our nanozyme vesicle exhibits excellent biocompatibility and stealth ability for long blood circulation. Together, we demonstrate that GQDzyme/ABTS based exosome-like nanozyme vesicle is an ideal nanoplatform for developing deep-tissue tumor-targeted catalytic PAI in vivo.

Nanozyme based tumor catalytic theranostics

2019 Fall National Meeting

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