Diffusion Reflection Method for Early Detection of Oral Squamous Cell Carcinoma Specifically Targeted by Circulating Gold-Nanorods Bio-Conjugated to Anti-Epidermal Growth Factor Receptor

Abstract

Background: Translation of nanomedical developments into clinical application is receiving an increasing interest. However, its use for oral squamous cell carcinoma (OSCC) diagnosis remains limited. We present an advanced nanophotonic method for oral cancer detection, based on diffusion reflection (DR) measurements of gold-nanorods bio-conjugated to anti-epidermal growth factor receptor (C-GNRs) specifically attached to OSCC cells. Objective: To investigate in a rat model of oral carcinogenesis the targeting potential of C-GNRs to OSCC by using the DR optical method. Materials and Methods: OSCC was induced by the carcinogen 4-nitroquinoline-N-oxide (4NQO). C-GNRs were introduced locally and systemically and DR measurements were recorded from the surface of the rat tongue following illumination with red laser beam. Rats were divided into experimental and control groups. The results were compared with the histologic diagnosis. Results: A total of 75 Wistar-derived rats were enrolled in the study. Local application did not reveal any statistical results. DR measurements following intravenous injection of C-GNRs revealed a significant increase in light absorption in rats with OSCC compare with rats without cancer (p<0.02, sensitivity 100%, specificity 89%). In addition, absorption of light increased significantly in cases of severe dysplasia and cancer (high risk) compared to rats without cancer and rats with mild dysplasia (low risk) (86% sensitivity and 89% specificity, AUC=0.79). Conclusion: Combining nanotechnology and nanophotonics for in vivo diagnosis of OSCC serves as additional tier in the translation of advanced nanomedical developments into clinical applications. The presented method shows a promising potential of nanophotonics for oral cancer identification, and provides support for the use of C-GNRs as a selective drug delivery.

Gold nanomaterials for oral cancer diagnosis and therapy: Advances, challenges, and prospects

“… Nanomaterial Size (nm) Principle Sample/target Effect Diagnosis ability in cancer vs control group Differences in abnormal vs normal group Ref. AuNSs AuNRs 13.6–17.2 1.3 ​× ​5.6 SPR Saliva/OPN Limit of detection ↑ 0.02 vs 0.14 0.03 vs 0.14 ​ng mL−1 / [ 39 ] AuNRs 13.72 ​× ​49.73 SERS Exfoliative cells/CAL-27 Specificity↑ Sensitivity↑ 100% vs 60% 100% vs 70% / [ 95 ] AuNPs 15 SERS Saliva/spectrum Potential to detect peaks / New peaks at 1097 and 1627 cm-1 in the cancer group [ 80 ] AuNPs 20 SERS Saliva/(S100P) mRNA S100P mRNA detection limited 10 ​nM (S100P) mRNA Three times higher in cancer group [ 96 ] AuNCs 15 OCT Hamster/cheek pouch tumor Visualization of tumor sites / OCT and DvOCT signal inversion [ 97 ] AuNPs 70 OCT Hamster/cheek pouch tumor Pinpointed pathological structures of early-stage oral cancer / Increase optical scattering intensity ​33% [ 98 ] AuNRs 15 ​× ​50 DR OSCC Sensitivity and specificity significant increase Sensitivity 100%, specificity 89% / [ 99 ]

Fig. 2 Early, sensitive, noninvasive, and rapid cancer screening based on AuNRs: (Ⅰ) The schematic diagram showed the preparation of SERS substrate and the SERS d...

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“…To achieve this goal, AuNPs are coupled to the anti-epidermal growth factor receptor ( anti -EGFR), which is a cell surface receptor belonging to the ErbB family of tyrosine kinases that play an important role in regulating cell proliferation [ 109 ]. Based on DR measurements of AuNRs bio-conjugated to anti -EGFR specifically attached to OSCC cells [ 99 ]. The DR measurements revealed a significant increase in light absorption in rats with OSCC compare with rats without cancer (p ​< ​0.02, sensitivity 100%, specificity 89%) [ 99 ].…”

“…Based on DR measurements of AuNRs bio-conjugated to anti -EGFR specifically attached to OSCC cells [ 99 ]. The DR measurements revealed a significant increase in light absorption in rats with OSCC compare with rats without cancer (p ​< ​0.02, sensitivity 100%, specificity 89%) [ 99 ]. The aforementioned studies indicate that the detection system based on AuNPs could be effective in the early detection of oral cancer.…”

Noninvasive Nanodiamond Skin Permeation Profiling Using a Phase Analysis Method: Ex Vivo Experiments

“…The small size of the fNDs enables their penetration into and through the deep skin layers. Studying the penetration profile of the NDs along the different skin layers can be done by using OCT, fluorescence confocal microscopy, FLIM, , and transmission electron microscopy (TEM) . In addition, histopathology ,, is a common technique for examining different skin layers.…”

Measurement of the Second-Order Polarizability of Silver Nanoparticles With Reference-Free Hyper-Rayleigh Scattering for Entangled Photon Pair Interaction

“…One suggested way to achieve stronger EPPI is to make use of metallic nanoparticles (NPs), whose localized surfaceplasmon resonance (LSPR) can enhance linear and nonlinear interactions [16][17][18][19][20]. Ashkenazy et al have described how the expected enhancement of EPPI (specifically, SHG) with NPs can be deduced from classical-light SHG measurements performed in a novel reference-free hyper-Rayleigh scattering (RFHRS) method [21,22].…”