Abstract
Detection and imaging of single cancer cells is critical for cancer diagnosis and understanding of cellular dynamics. Photoacoustic imaging (PAI) provides a potential tool for the study of cancer cell dynamics, but faces the challenge that most cancer cells lack sufficient endogenous contrast. Here, a type of colloidal gold nanoparticles (AuNPs) are physically fabricated and are precisely functionalized with quantitative amounts of functional ligands (i.e., polyethyleneglycol (PEG) and (Arginine(R)–Glycine(G)–Aspartic(D))4 (RGD) peptides) to serve as an exogenous contrast agent for PAI of single cells. The functionalized AuNPs, with a fixed number of PEG but different RGD densities, are delivered into human prostate cancer cells. Radioactivity and photoacoustic analyses show that, although cellular uptake efficiency of the AuNPs linearly increases along with RGD density, photoacoustic signal generation efficiency does not and only maximize at a moderate RGD density. The functionalization of the AuNPs is in turn optimized based on the experimental finding, and single cancer cells are imaged using a custom photoacoustic microscopy with high‐resolution. The quantitatively functionalized AuNPs together with the high‐resolution PAI system provide a unique platform for the detection and imaging of single cancer cells, and may impact not only basic science but also clinical diagnostics on a range of cancers.
Highlights
Cancer is a group of fatal diseases that involve abnormal cell proliferation with the potential to invade and spread to other parts of the body.[1]
To address the problems of high-sensitivity detection and high-resolution imaging of single or small populations of cancer cells, we physically produced a kind of colloidal AuNPs with bare surfaces using ultrafast laser ablation of a gold target immersed in deionized water, precisely coated them with quantitative amounts of two different functional ligands, i.e. thiol-terminated polyethylene glycol (PEG) molecules and cysteine-modified (Arginine(R)-Glycine(G)-Aspartic(D))4 (RGD) peptides, and selectively delivered them into human prostate cancer cells to serve as an exogenous absorption contrast
We studied the dependence of cellular uptake efficiency of the functionalized AuNPs (fAuNPs) on the surface RGD density using radioactivity analysis.[46, 47]
Summary
Cancer is a group of fatal diseases that involve abnormal cell proliferation with the potential to invade and spread to other parts of the body.[1]. Carcinoma,[12] breast cancer,[13] and circulating tumor cells.[14,15,16] Several parameters, such as size, shape, and surface chemistry, are critical for their photoacoustic applications.[34] While the size and shape determine the optical properties, the surface chemistry controls the interactions of AuNPs with surrounding biological environments.[30, 35] To achieve highly efficient delivery of AuNPs into cancer cells, active surface coating with functional ligands, such as hydrophilic polymers and targeting molecules, are required. To address the problems of high-sensitivity detection and high-resolution imaging of single or small populations of cancer cells, we physically produced a kind of colloidal AuNPs with bare surfaces using ultrafast laser ablation of a gold target immersed in deionized water, precisely coated them with quantitative amounts of two different functional ligands, i.e. thiol-terminated polyethylene glycol (PEG) molecules and cysteine-modified (Arginine(R)-Glycine(G)-Aspartic(D)) (RGD) peptides, and selectively delivered them into human prostate cancer cells to serve as an exogenous absorption contrast. Based on the experimental results, we determined the optimal RGD ligand density that yields the highest photoacoustic signal amplitude, and imaged individual cancer cells using a custom high-resolution photoacoustic microscopy (PAM) system
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