A Platinum-Protein hybrid nanostructure enables both targeted cancer theragnosis and platinum clearance

Considering the fundamental advantages of photothermal therapy (PTT) and photoacoustic imaging (PAI) of cancer such as precise spatiotemporal control-based, non-invasive therapy with negligible drug resistance and side effects and sensitive, specific diagnosis with high spatial resolution at substantial depth, an advanced, or clinically feasible material that enables both PTT and PAI surely needs to be developed but remains a major challenge yet. Here we developed a hybrid nanostructure (PtNC@ABP-HBVC) between plasmonic platinum nanocluster (PtNC) comprised of many tiny Pt nanoparticles (PtNPs, ∼ 3 nm that is small enough to pass through glomerular filtration in kidney) and a specially designed protein scaffold (ABP-HBVC) capable of binding to human serum albumin (HSA). PtNC is beneficial for efficient light-to-heat conversion and acoustic wave generation due to plasmonic coupling effect among the small PtNPs, and the HSA binding to ABP-HBVC significantly lowers immunogenicity and enables PtNC to be effectively delivered to tumor. Using human breast cancer-bearing xenograft mice, we demostrated that PtNC@ABP-HBVC has the superior efficacy in targeted cancer theragnosis (PTT + PAI) and is rapidly cleared from the body through urinary excretion, which shows its great potential as a promising, clinically attractive agent for cancer theragnosis.