Bioinspired Tumor Calcification‐Guided Early Diagnosis and Eradication of Hepatocellular Carcinoma

Author:

Bai Shuang12,Chen Hu1,Fu Shiying3,Liu Chao14,Gao Xing3,Li Shuo1,Chen Yulun5,Lan Yulu1,Xia Yutian1,Dai Qixuan1,He Pan1,Zhang Yang1,Zhao Qingliang1,Mao Jingsong15,Lu Zhixiang14,Liu Gang13ORCID

Affiliation:

1. State Key Laboratory of Infectious Disease Vaccine Development Xiang An Biomedicine Laboratory & Center for Molecular Imaging and Translational Medicine School of Public Health Xiamen University Xiamen 361102 China

2. Shaanxi Province Center for Regenerative Medicine and Surgery Engineering Research the First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China

3. State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Biology School of Life Sciences Xiamen University Xiamen 361102 China

4. School of Pharmaceutical Sciences Xiamen University Xiamen 361102 China

5. Department of Radiology Xiang'an Hospital of Xiamen University Xiamen 361102 China

Abstract

AbstractTumor calcification is found to be associated with the benign prognostic, and which shows considerable promise as a somewhat predictive index of the tumor response clinically. However, calcification is still a missing area in clinical cancer treatment. A specific strategy is proposed for inducing tumor calcification through the synergy of calcium peroxide (CaO2)‐based microspheres and transcatheter arterial embolization 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 that enables clear localization of the in vivo tumor site and partial delineation of tumor margins in an orthotopic HCC rabbit model. This osmotic calcification can facilitate tumor clinical diagnosis, which is of great significance in differentiating tumor response during early follow‐up periods. Proteome and phosphoproteome analysis identify that calreticulin (CALR) is a crucial target protein involved in tumor calcioptosis. Further fluorescence molecular imaging analysis also indicates that CALR can be used as a prodromal marker of calcification to predict tumor response at an earlier stage in different preclinical rodent models. These findings suggest that upregulated CALR in association with tumor calcification, which may be broadly useful for quick visualization of tumor response.

Funder

Major State Basic Research Development Program of China

Program for New Century Excellent Talents in University

Excellent Young Scientists Fund

National Natural Science Foundation of China

Publisher

Wiley

Subject

Mechanical Engineering,Mechanics of Materials,General Materials Science

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