Bioinspired Tumor Calcification-Guided Early Diagnosis and Eradication of Hepatocellular Carcinoma.

Tumor calcification was found to be associated with the benign prognostic, and which showed considerable promise as a somewhat predictive index of the tumor response clinically. However, calcification is still a missing area in clinical cancer treatment. We propose a specific strategy for inducing tumor calcification through the synergy of CaO 2 -based microspheres and transcatheter arterial embolization (TAE) for the treatment of hepatocellular carcinoma (HCC). The persistent calcium stress in situ specifically leads to powerful tumor calcioptosis, resulting in diffuse calcification and a high-density shadow on computed tomography (CT) that enables clear localization the in vivo tumor site and partial delineation of tumor margins in an orthotopic HCC rabbit model. This osmotic calcification could facilitate tumor clinical diagnosis, which is of great significance in differentiating tumor response during early follow-up periods. Proteome and phosphoproteome analysis identified that calreticulin (CALR) is a crucial target protein involved in tumor calcioptosis. Further fluorescence molecular imaging analysis also indicated that CALR can be used as a prodromal marker of calcification to predict tumor response at an earlier stage in different preclinical rodent models. Our findings suggest that upregulated CALR in association with tumor calcification, which might be broadly useful for quick visualization of tumor response. This article is protected by copyright. All rights reserved.