Gold is a Nobel metal with outstanding optical properties at the nanoscale. Michael Faraday’s gold colloid (1856) is considered the first preparation of AuNP which is currently on display in Faraday Museum (The Royal Institution, London, UK) [40]. After a century and a half, chemists and physicists developed tremendous wealth of knowledge on the synthesis of much more sophisticated gold nanostructures and fundamentals to understand their optical and photothermal properties [2,19,20,21,22,23].

The optical properties of AuNP arise from the exceptional interaction between photons and electrons of gold at the nanoscale. In more details, the incident photons excite electrons in the conduction band of AuNP resulting in collective oscillation of these electrons to match the wavelength of the incident photons and then the resonating oscillation results in optical extinction (the sum of both optical absorption and scattering). This phenomenon is termed as the Localized surface plasmon resonance (LSPR) and typically observed for AuNP when excited with light with a wavelength in the Visible-near infrared region (Vis-NIR) of the spectrum [41]. LSPR explain the brilliant color of suspensions of AuNP [2]. For example, when spherical AuNP with a diameter of 18 nm is excited with white light, it appears red as these AuNP absorb the blue and green fractions and leave the red counterpart for external eyes to see. The UV-vis spectrum of the same AuNP typically exhibit a plasmonic absorption maximum around the 520 nm. The optical properties of the same AuNP will significantly change if we change the particle’s diameter, shape, refractive index of the medium or the aggregation state. This explains why as suspension of AuNP with a diameter of 100 nm appears blue and not red. For gold nanorods (AuNR), excited electrons have two probabilities to oscillate: (1) around the shorted axis resulting in a transverse plasmon mode with a plasmonic absorption maximum around 520 nm; (2) around the longer axis resulting in a longitudinal plasmon mode with a plasmonic absorption maximum in the far visible to the NIR (650–1200 nm) depending on the ratio of the length to the width of the AuNR. The strong absorption of AuNR and other anisotropic gold-based nanostructures is highly advantageous for photothermal application considering the deeper light penetration in biological tissue in the NIR region. The absorbed optical energy by AuNP finally decays as a local thermal energy to their close proximity of the excited nanoparticles. For example, cancer cells can be ablated by the uptake of AuNP if excited by the proper light as a result of the generated heat near to the surface of the nanoparticle. It worth to mention that the first clinical trial on human to evaluate the effectiveness of gold-silica nanoshells in ablating prostate cancer were conducted recently and resulted in a promising result [42].

Similar to many other types of inorganic nanomaterials, AuNP could be prepared via top-down or bottom-up approaches [43]. In case of the top-down approach, physical methods are employed to erode a bulk gold into AuNP including laser ablation [44], aerosol technology [45], UV and IR irradiation [46], and ion sputtering [47]. By contrast, synthesis of AuNP via the bottom-up approach starts from the atomic level (gold ions) and builds up to reach nanoparticles at a desired size and shape employing proper chemistries. Chemical techniques to prepare spherical AuNP relies on the reduction of Au ions using proper reducing agents in the presence of capping agents [48]. Currently, these reactions are well established and mechanistic perspectives as well as variables to control the resulting AuNP are well identified. Examples of widely employed chemical protocols to prepare AuNP are the Frens/Turkevich method (for 10–100 nm hydrophilic spherical AuNP) [49,50], the Brust method (for 1–3 nm spherical hydrophobic AuNP) [51], the Murphy/El-Sayed surfactant assessed seed-mediated method (for gold nanorods) [52,53,54,55] and the polyol-galvanic method (to prepare gold hollow polyhedral nanoparticles) [56,57]. Other modified protocols and green chemistry-based routes are available in the literature as well [58,59,60,61]. Collectively, AuNP enjoy the availability of well optimized, reproducible, tunable synthetic routes to prepare a library of AuNP with various sizes and shapes using simple chemistries. Currently, AuNP with variable size, shape and surface chemistry can be ordered from various commercial suppliers.

AuNP were applied in various biomedical applications including imaging, diagnosis, therapeutics, and drug delivery, as summarized in Figure 1 [35,62,63,64,65]. The unique optical properties of AuNP are the origin and the basis of various sensing and imaging applications. For example, the extensive and tunable light absorption of AuNP is the key in the early used lateral flow rapid test strip that are available globally in community pharmacy and in use for six decades to detect and test the level of human chorionic gonadotropic in women’s urine. Optical responses upon AuNP aggregation or changing the local refractive index are another bases of many optical-based sensing applications of AuNP. When AuNP aggregate or even de-aggregate, they exhibit extremely different optical properties and this explain why adding salt to ruby red suspension of AuNP turns it quickly to blue upon aggregation. Explanation of these intriguing optical responses and applications in sensing are thoroughly discussed in available review contributions in the literature [66,67,68].

Away from optical absorption, the extensive elastic light scattering from AuNP can be employed in various optical scattering-based sensing applications. AuNP are excellent light scattering agents in the Vis-NIR and they appear as bright stars under dark field microcopy mode. These optical properties were employed to localize and track these tinny nanoparticles using dark field microscopy [69,70,71]. Targeted AuNP that can recognize and bind specifically to specific markers on cells and can be used as a reporters to sense and visualize the targeted cells under dark field microscopy [72]. AuNP are excellent enhancers to both fluorescence excitation and vibrational Raman scattering. In fact, fluorophore or Raman active tags experience a tremendous enhancement in their fluorescence and vibrational signals, respectively, if they are placed in the proper distance from AuNP. These enhancements are the bases of many other brilliant sensing platforms and applications and excellent reviews covering these fields are available in the literature [73,74,75,76,77].

Other advantages of AuNP are the ease of visualization using electron microscopy and quantification using mass spectrometry (ICP-MS: inductively coupled plasma-mass spectrometry) with very high sensitivity and low intrinsic background levels in biological samples. We have utilized this attribute to label polymeric nano-host and track their localization inside a single cancer cell [35]. The ease of preparation in various sizes/shapes, surface modification, visualization and quantification make AuNP as “ideal” nanoprobes to understand the fate of nanoparticles, their biodistribution and pharmacokinetics parameters in vitro and in vivo [14,78].

Anisotropic AuNP that display strong plasmonic absorption in the Vis-NIR and strong photothermal conversion has been explored as potential candidates to fight cancer. The ability to manipulate the surface of these “nano-heaters” is a clear advantage to control their distribution in living organisms and accumulation into cancer regions. From the first pioneering work on utilizing AuNR to ablate cancer cells in vitro [79,80,81] twenty years ago all the way to the recent first clinical trial on human [42], the literature is rich of outstanding reviews on the photothermal effect of gold nanostructures and its fundamentals and applications [11,13,82,83,84,85,86,87,88,89,90].