Reversing the Chirality of Surface Ligands Can Improve the Biosafety and Pharmacokinetics of Cationic Gold Nanoclusters

Tang, Hao; Li, Qizhen; Yan, Weixiao; Jiang, Xingyu

2021-05-01

10.1002/anie.202101609

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   影响因子和分区

1433-7851

1521-3773

Severe toxicity and rapid in vivo clearance of cationic nanomaterials seriously hinder their clinical translation. Present strategies to improve the biosafety and in vivo performance of cationic nanomaterials require neutralization of positive charge, which often compromises their efficacy. Herein, we report that substituting L-glutathione (L-GSH) on cationic gold nanoclusters (GNCs) with its D-counterpart can effectively improve the biosafety and pharmacokinetics. Compared with L-GNCs, D-GNCs do not exhibit cellular cytotoxicity, hemolysis, or acute damage to organs. Cationic D-GNCs show less cell internalization than L-GNCs, and do not induce cellular apoptosis. In vivo, the chirality of surface ligands distinctly affects the pharmacokinetics and tumor targeting abilities of D-/L-GNCs. D-GNCs show higher extended circulation time in blood plasma compared to similarly-sized and poly (ethylene glycol)-modified gold nanoparticles. This work demonstrates that the choice of chirality of surface ligands can determine toxicities and pharmacokinetics of cationic nanomaterials.

Cationic gold nanoclusters Chirality Pharmacokinetics Toxicity

SCI ; EI

英语

NI论文

第一 ; 通讯

National Key R&D Program of China[2018YFA0902600] ; Shenzhen Science and Technology Program[KQTD20190929172743294] ; National Natural Science Foundation of China[21535001,81730051,81673039] ; Chinese Academy of Sciences["QYZDJ-SSW-SLH039","121D11KYSB20170026"] ; Shenzhen Bay Laboratory[SZBL2019062801004] ; Guangdong Innovative and Entrepreneurial Research Team Program[2019ZT08Y191]

Chemistry

Chemistry, Multidisciplinary

WOS:000649416900001

WILEY-V C H VERLAG GMBH

20212010355498

Biohazards ; Blood ; Cell death ; Chirality ; Gold Nanoclusters ; Gold nanoparticles ; Nanoclusters ; Nanostructured materials ; Pharmacokinetics ; Polyethylene glycols ; Toxicity

Bioengineering and Biology:461 ; Nanotechnology:761 ; Physical Chemistry:801.4 ; Organic Polymers:815.1.1 ; Accidents and Accident Prevention:914.1 ; Atomic and Molecular Physics:931.3 ; Solid State Physics:933

CHEMISTRY

Web of Science

Southern Univ Sci & Technol, Dept Biomed Engn, 1088 Xueyuan Rd, Shenzhen 518055, Guangdong, Peoples R China

Tang, Hao,Li, Qizhen,Yan, Weixiao,et al. Reversing the Chirality of Surface Ligands Can Improve the Biosafety and Pharmacokinetics of Cationic Gold Nanoclusters[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2021,60:13829-13834.

Tang, Hao,Li, Qizhen,Yan, Weixiao,&Jiang, Xingyu.(2021).Reversing the Chirality of Surface Ligands Can Improve the Biosafety and Pharmacokinetics of Cationic Gold Nanoclusters.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,60,13829-13834.

Tang, Hao,et al."Reversing the Chirality of Surface Ligands Can Improve the Biosafety and Pharmacokinetics of Cationic Gold Nanoclusters".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 60(2021):13829-13834.