Journal
ACS APPLIED BIO MATERIALS
Volume 4, Issue 1, Pages 742-751Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.0c01303
Keywords
sintering; autofluorescence; persistent luminescence; acidosis; alpha-helix
Funding
- University Grants Commission (UGC), New Delhi
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In this study, zinc gallate-based persistent luminescence nanoparticles coated with a variant of pH-low-insertion peptide (pHLIP) were developed for cancer detection and diagnosis. Results indicated that these nanoparticles exhibited faster and more precise uptake in the acidic tumor environment compared to other organs. Experiments on mice showed successful tumor targeting within a short period of time.
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.
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