<i>In Vivo</i> Aggregation of Clearable Bimetallic Nanoparticles with Interlocked Surface Motifs for Cancer Therapeutics Amplification

Although renal-clearable luminescent metal nanoparticles (NPs) have been widely developed, their application to efficient cancer therapy is still limited due to low reactive oxygen species (ROS) production. Here, a novel system of clearable mercaptosuccinic acid (MSA) coated Au-Ag bimetallic NPs is designed to enhance ROS production. The results show that the strong COO-Ag coordination bonds between the carboxylic acid groups of MSA and Ag atoms on the Au-Ag bimetallic NPs could construct high-rigidity interlocked surface motifs to restrict the intrananoparticle motions for enhanced ROS generation. Moreover, bimetallic NPs exhibit pH-responsive self-assembly capability under the acidic environment inside lysosomes of cancer cells at both <i>in vitro</i> and <i>in vivo</i>, restricting the internanoparticle motions to further boost ROS production. The well-designed bimetallic NPs show high tumor targeting efficiency, fast elimination from the body through rapid liver biotransformation, and extensive destruction to cancer cells, resulting in good security and prominent therapeutic performance.