Abstract

Prostate cancer is one of the male killing diseases and early detection of prostate cancer is the key for better treatment and lower cost. However, the number of prostate cancer cells is low at the early stage, so it is very challenging to detect. In this study, we successfully designed and developed upconversion immune-nanohybrids (UINBs) with sustainable stability in a physiological environment, stable optical properties and highly specific targeting capability for early-stage prostate cancer cell detection. The developed UINBs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS) and luminescence spectroscopy. The targeting function of the biotinylated antibody nanohybrids were confirmed by immunofluorescence assay and western blot analysis. The UINB system is able to specifically detect prostate cancer cells with stable and background-free luminescent signals for highly sensitive prostate cancer cell detection. This work demonstrates a versatile strategy to develop UCNPs based sustainably stable UINBs for sensitive diseased cell detection.

Highlights

  • Precision medicine including sensitive early-stage cancer detection holds promising potentials for lower healthcare cost and better treatment outcomes[1,2,3]

  • The excitation of traditional biolabels usually requires the use of UV or short wavelength radiation for the down conversion photon transfer, which results in a series of drawbacks including low signal-to-noise ratio due to background auto fluorescence, low light-penetration depth inherent to the short wavelength of the UV excitation light, and potential cellular damage caused by long-term irradiation[15,16,17]

  • The results showed that the cell viability was above 90% over 48 h exposure to up to 200 g/mL of the conjugated Upconversion nanoparticles (UCNPs) (Supplementary Figure S5), demonstrating good biocompatibility

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Summary

Introduction

Precision medicine including sensitive early-stage cancer detection holds promising potentials for lower healthcare cost and better treatment outcomes[1,2,3]. Many commercially available bioreagents including organic dyes, chelates and fluorescent proteins have already been employed in cancer imaging and theranostics as conventional biolabels[8,9] Their application in high sensitivity disease detection has been seriously hindered by some disadvantages, including undesirable photobleaching and photoblinking, chemical and metabolic degradation, and low signal to noise ratio[10,11]. A variety of targeting molecules such as proteins and peptides need to be conjugated onto the surface of UCNPs for specific cell recognition, towards super sensitive disease detection[36,37] To this end, various surface modification and functionalization strategies have been investigated to transfer such passivated nanocrystals from organic solution into aqueous solutions and to impart them targeting capability for various biomedical applications[38].

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