Photoacoustic detection and imaging of single cancer cells with peptide conjugated gold nanoparticles
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AbstractPhotoacoustic imaging (PAI), which is based on the conversion of light into sound, is an emerging, hybrid and noninvasive imaging modality with highly scalable resolution. PAI has shown tremendous potential in early tumor detection and imaging by providing structural, functional and metabolic information. But to date, most work has been focused on tumor detection at the macroscopic level (i.e. tissue, organ). For early tumor diagnosis, microscopic detection of individual cancer cells is highly desirable and of special significance. However, detection and imaging of single cancer cells using PAI is very challenging because most cancer cells are colorless, thus exhibiting little endogenous contrast. Gold nanoparticles (AuNPs), which have good biocompatibility, low toxicity and high optical absorption, are an exogenous contrast agent that can facilitate PAI of single cancer cells.In this study, we synthesized peptide-conjugated AuNPs to selectively target DU145 human prostate cancer cells, and employed a laser-scanning photoacoustic microscopy (PAM) to detect and image individual cells. The used AuNPs had an average diameter of 30 nm and were physically fabricated by ultrafast pulsed laser ablation of gold target in ultrapure water. Their surface chemistry was modified through a sequential conjugation process, in which a predetermined amount of thiolated PEG 5000 molecules and RGD peptides were successively bound to the AuNPs with quantitative control and high efficiency. After incubation with DU145 cells, the functionalized PEG-RGD-AuNPs were endocytosed with the help of membrane receptors and produced sharp absorption contrast. The internalized AuNPs generated strong photoacoustic signals after absorbing excitation laser and the signals were captured by a highly sensitive hydrophone to form cell images.Combing functional AuNPs and high-resolution PAM, we successfully detected and imaged single, live DU145 cancer cells. Though transparent, the cancer cells were visibly delineated by intracellular AuNPs and were clearly distinguishable. Moreover, to achieve optimum detection efficiency, we also studied the relationship between the density of RGD peptide and the amplitude of photoacoustic signal. Experimental results reveal that, although the amount of cellular uptake of AuNPs was proportional to RGD density (from radioactivity analysis using a Gamma counter), the amplitude of photoacoustic signal did not. Photoacoustic detection efficiency reached a maximum when the molar ratio of RGD peptides to AuNPs was approximately 1000.To our best knowledge, this is the first report on photoacoustic detection and imaging of specific cancer cells using peptide-conjugated AuNPs at single-cell resolution. By translating PAI from macro to micro, the work is expected to open a new avenue for early cancer detection, imaging, diagnosis and even treatment.Citation Format: Chao Tian, Wei Qian, Xia Shao, Zhixing Xie, Xu Cheng, Shengchun Liu, Qian Cheng, Bing Liu, Xueding Wang. Photoacoustic detection and imaging of single cancer cells with peptide-conjugated gold nanoparticles. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-191.
