An Artificial Signaling Pathway Primitive-based Intelligent Biomimetic Nanoenzymes Carrier Platform for Precise Treatment of Her2 (+) Tumors

In tumor treatment, the deposition of nanoenzymes in normal tissues and cause potential side effects are unavoidable. Here, we designed an intelligent biomimetic nanoenzymes carrier platform (MSC) that endows the carrier platform with "wisdom" by introducing Affibody-Notch(core)-VP64-GAL4/UAS-HSV-TK artificial signal pathways to mesenchymal stem cells (MSCs). This intelligent nanoenzymes carrier platform is distinguished from the traditional targeting tumor microenvironment or enhancing affinity with tumor, which endue MSC with tumor signal recognition capacity, so that MSC can autonomously distinguish tumor from normal tissue cells and feedback edited instructions. In this study, MSC can convert tumor signals into HSV-TK instructions through artificial signal pathway after recognizing Her2 (+) tumor. Subsequently, the synthesized HSV-TK can rupture MSC under the mediation of ganciclovir, and release the preloaded Cu/Fe nanocrystal clusters to kill the tumor accurately. Meanwhile, MSC without recognizing tumors will not initiate the HSV-TK instructions, thus being unresponsive to GCV and blocking the release of nanoenzymes in normal tissues. Consequently, MSC is the first intelligent biomimetic nanoenzymes carrier platform, which represents a new biomimetic nanoenzymes targeting mode.