pH-(Low)-Insertion Peptide-Assisted Detection and Diagnosis of Cancer Using Zinc Gallate-Based Persistent Luminescence Nanoparticles

For developing nanoformulations to detect and diagnose cancer, zinc gallate (ZGO)-based persistent luminescence nanoparticles (NPs) coated with an in-house-synthesized variant of pH-low-insertion peptide (pHLIP) were developed. Initially, Cr3+-doped ZGO-NPs were prepared and functionalized to obtain ZGO-maleimide NPs. These ZGO-maleimide NPs were conjugated to the variant of pHLIP, yielding ZGO-pHLIP. The ZGO-NPs and ZGO-pHLIP showed maximum luminescence when excited at 254 nm. Further, ZGO-pHLIP was evaluated for cytotoxicity against MCF-7 cancer cells. A lactate dehydrogenase assay confirmed efficient internalization of ZGO-pHLIP with temporary distortion of the cell membrane. The targeting of ZGO-pHLIP to 4T1-FL2 tumor transplanted in CD1 nude mice exhibited their accumulation in the tumor, monitored by a photon imager (initially at 6 h and then exposed to a red-light-emitting diode (LED) for 1 min and remonitored until 24 h). Results revealed that targeting of the tumor by ZGO-pHLIP was achieved in 6 h. Imaging studies of visceral organs were performed ex vivo. Throughout studies, there was no evidence of cytotoxicity or distress in mice. Our studies show faster and precise uptake of ZGO-pHLIP in the acidic tumor environment over other organs.