Abstract

Mitochondrion has emerged as a promising drug target for photodynamic therapy (PDT), due to its significant role in supporting life activities and being reactive oxygen species (ROS)-sensitive. Herein, we establish a new strategy that in-situ bio-synthesized Au NCs combine with mitochondria-targeted aptamer-Pyro conjugates (ApPCs) for specific tumor imaging and PDT. The prepared ApPCs can serve as template for the in-situ bio-synthesis of Au NCs, thereby facilitating the generation of Au NCs-ApPCs assemblies in unique tumor microenvironment . Compared with highly negatively charged ApPCs, bio-synthesized nanoscale Au NCs-ApPCs assemblies are conducive to cell uptake, which consequently benefits the delivery of ApPCs. After dissociated from Au NCs-ApPCs, internalized ApPCs can selectively accumulate in mitochondria and generate excess ROS to disrupt the mitochondrial membrane upon irradiation, thus inducing efficient cell killing. In vitro assays demonstrated that the fluorescent Au NCs-ApPCs assemblies could be specifically produced in cancerous cells, indicating the specific tumor imaging ability, while intracellular ApPCs co-localized well with mitochondria. CCK-8 results revealed over 80% cell death after PDT. In vivo study showed that fluorescent Au NCs-ApPCs assemblies were exclusively generated in tumor and achieved long-term retention; tumor growth was significantly inhibited after 15-day PDT treatment. All these evidences suggest that in-situ bio-synthesized Au NCs-ApPCs assembly is a potent mitochondria-targeted nanoprobe to boost the PDT efficacy of cancers.