TY - JOUR

T1 - Highly Hydrated Paramagnetic Amorphous Calcium Carbonate Nanoclusters as a Superior MRI Contrast Agent

AU - Dong, Liang

AU - Xu, Yun-Jun

AU - Sui, Cong

AU - Zhao, Yang

AU - Mao, Li-Bo

AU - Gebauer, Denis

AU - Rosenberg, Rose

AU - Avaro, Jonathan

AU - Wu, Ya-Dong

AU - Gao, Huai-Ling

AU - Pan, Zhao

AU - Wen, Hui-Qin

AU - Yan, Xu

AU - Li, Fei

AU - Lu, Yang

AU - Cölfen, Helmut

AU - Yu, Shu-Hong

N1 - This work was supported by the National Natural Science Foundation of China (Grants 51732011 and U1932213 to S.H.Y.; 22122502 and 51972090 to Y.L.; 51702309 to L.D.; 81801831 to H.Q.W.), the National Key Research and Development Program of China (Grants 2021YFA0715700 and 2018YFE0202201) to S.H.Y., the Fundamental Research Funds for the Central Universities (WK9110000062 to Y.J.X.; WK2060190056 to L.D.), the University Synergy Innovation Program of Anhui Province (Grant GXXT-2019-028) to S.H.Y., Science and Technology Major Project of Anhui Province (201903a05020003) to S.H.Y., the Natural Science Foundation of Anhui Province (2008085J06 to Y.L.; 1708085ME114 to Y.J.X.), the China Postdoctoral Science Foundation (2015M570540) to L.D., the Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology (2016FXZY005) to Y.L. The authors would like to thank Mei Sun, Yan-Wei Ding, Cheng-Min Wang, Yu-Song Wang, Guan-Yin Gao, Han-Bao Chong, Yu-Feng Meng, Yang-Yi Liu in University of Science and Technology of China, Hao Ding in Suzhou Niumag Analytical Instrument Corporation, Yong-Hong Song, Wen-Shu Wu in Hefei University of Technology, Hai-Shen Qian in Anhui Medical University, He Chen, Li Zhang and Hui Wang in The First Affiliated Hospital of Anhui Medical University, Kun Liu in Xiamen University, Duo An in Cornell University, and Ye-Ping Li from Anton Paar China for useful assistance of this manuscript, and Luca Olivi, Giuliana Aquilanti and Simone Pollastri in the XAFS beamline at Elettra Synchrotron for their help. D.G. is a professor of the Leibniz Universität Hannover. J. A. is financed within the framework of the SFB 1214 (Collaborative Research Center funded by the German Research Foundation, DFG, project A02). H.C. thanks the particle analysis center of the SFB 1214 for the AUC equipment.

PY - 2022/8/29

Y1 - 2022/8/29

N2 - Amorphous calcium carbonate plays a key role as transient precursor in the early stages of biogenic calcium carbonate formation in nature. However, due to its instability in aqueous solution, there is still rare success to utilize amorphous calcium carbonate in biomedicine. Here, we report the mutual effect between paramagnetic gadolinium ions and amorphous calcium carbonate, resulting in ultrafine paramagnetic amorphous carbonate nanoclusters in the presence of both gadolinium occluded highly hydrated carbonate-like environment and poly(acrylic acid). Gadolinium is confirmed to enhance the water content in amorphous calcium carbonate, and the high water content of amorphous carbonate nanoclusters contributes to the much enhanced magnetic resonance imaging contrast efficiency compared with commercially available gadolinium-based contrast agents. Furthermore, the enhanced T 1 weighted magnetic resonance imaging performance and biocompatibility of amorphous carbonate nanoclusters are further evaluated in various animals including rat, rabbit and beagle dog, in combination with promising safety in vivo. Overall, exceptionally facile mass-productive amorphous carbonate nanoclusters exhibit superb imaging performance and impressive stability, which provides a promising strategy to design magnetic resonance contrast agent.

AB - Amorphous calcium carbonate plays a key role as transient precursor in the early stages of biogenic calcium carbonate formation in nature. However, due to its instability in aqueous solution, there is still rare success to utilize amorphous calcium carbonate in biomedicine. Here, we report the mutual effect between paramagnetic gadolinium ions and amorphous calcium carbonate, resulting in ultrafine paramagnetic amorphous carbonate nanoclusters in the presence of both gadolinium occluded highly hydrated carbonate-like environment and poly(acrylic acid). Gadolinium is confirmed to enhance the water content in amorphous calcium carbonate, and the high water content of amorphous carbonate nanoclusters contributes to the much enhanced magnetic resonance imaging contrast efficiency compared with commercially available gadolinium-based contrast agents. Furthermore, the enhanced T 1 weighted magnetic resonance imaging performance and biocompatibility of amorphous carbonate nanoclusters are further evaluated in various animals including rat, rabbit and beagle dog, in combination with promising safety in vivo. Overall, exceptionally facile mass-productive amorphous carbonate nanoclusters exhibit superb imaging performance and impressive stability, which provides a promising strategy to design magnetic resonance contrast agent.

UR - http://www.scopus.com/inward/record.url?scp=85136853692&partnerID=8YFLogxK

U2 - 10.21203/rs.3.rs-598198/v1

DO - 10.21203/rs.3.rs-598198/v1

M3 - Article

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5088

ER -