Multifunctional gold nanoparticles for diagnosis and therapy of disease

Abstract

Gold nanoparticles (AuNPs) have a number of physical properties that make them appealing for medical applications. For example, the attenuation of X-rays by gold nanoparticles has led to their use in computed tomography imaging and as adjuvants for radiotherapy. AuNPs have numerous other applications in imaging, therapy and diagnostic systems. The advanced state of synthetic chemistry of gold nanoparticles offers precise control over physicochemical and optical properties. Furthermore gold cores are inert and are considered to be biocompatible and nontoxic. The surface of gold nanoparticles can easily be modified for a specific application, and ligands for targeting, drugs or biocompatible coatings can be introduced. AuNPs can be incorporated into larger structures such as polymeric nanoparticles or liposomes that deliver large payloads for enhanced diagnostic applications, efficiently encapsulate drugs for concurrent therapy or add additional imaging labels. This array of features has led to the aforementioned applications in biomedical fields, but more recently in approaches where multifunctional gold nanoparticles are used for multiple methods, such as concurrent diagnosis and therapy, so-called theranostics. This review covers basic principles and recent findings in gold nanoparticle applications for imaging, therapy and diagnostics, with a focus on reports of multifunctional AuNPs.

Figure 1

Examples of different gold nanostructures (A) and examples of engineering of biocompatible gold nanoparticles through coating or encapsulation into carriers (B). (C) Aschematic depiction of gold nanoparticles for in vivo use. Figure adapted, with permission, from references ^{, , –}.

Figure 2

Gold nanoparticles functionalized with Gd for dual modality imaging (SRCT and MRI). (A) The nanoparticle design with SRCT and MR images of vials of the agent to the left and right. (B) SRCT of a rat before (t = −2 min) and after injection (t = 30 min) of the AuNPs. (C) MR images of a rat before (t = −5 min) and after injection (t = 30 min) of the AuNPs. Abbreviations: B for bladder, K for kidneys, WC for the tube collecting the urine. Figure adapted, with permission, from reference .

Figure 3

A) A schematic depiction of a multimodality contrast agent with Au core providing contrast for CT and additional labels for fluorescent imaging (Rhodamine) and MRI (Gd) in the phospholipid coating. Fluorescence (B), CT (C) and MRI (D) phantoms demonstrating the contrast generating properties of the nanoparticle. E) MR images of an atherosclerotic mouse aorta pre- and 24 hours post-injection with AuNPs. F) Confocal microscopy image of the atherosclerotic plaque of a mouse, where nanoparticles are red, macrophages are green and nuclei are blue. Arrowheads indicate colocalization of nanoparticles and macrophages. Figure adapted, with permission, from reference .

Figure 4

In vivo photoacoustic imaging of stem cells via labeling with AuNPs. (A–D) Ultrasound, photoacoustic, ultrasound/photoacoustic overlay, and ultrasound/spectroscopic images of gel encapsulated stem cells labeled with AuNPs injected into a rat hind limb. (E–H) Corresponding images of a rat hind limb without injection. Figure adapted, with permission, from reference .

Figure 5

A) Schematic depiction of gold nanoparticles functionalized with biotin, Rhodamine and paclitaxel (PTX) for cancer therapy. B) Cell mortality upon incubation with functionalized AuNPs. C) Dark field microscopy images of cells incubated with AuNPs. Figure adapted, with permission, from reference .

Figure 6

Gold nanoparticles for imaging and gene silencing therapy. (A) Design of the nanoparticle. Upon hydrolysis under low pH, the nanoparticle releases the siRNA cargo. (B) Three dimensional optical coherence tomography images of the nanoparticles generated with AuNPs (lower intensity image on the right confirms NP disintegration at lower pH). (C) Fluorescence microscopy of eGFP-expressing NIH 3T3 cells reveals gene silencing when incubated with AuNP-siRNA at low pH. Figure adapted, with permission, from reference .

Figure 7

AuNRs used for both imaging and therapy. A) Schematic depiction of photothermal heating of AuNRs. B) A three dimensional rendering of CT images of a mouse bearing two tumors on its chest, which had been injected with AuNRs. The location of the AuNRs is highlighted in red. C) Infra-red imaging of the mouse after NIR laser irradiation indicated the photothermal effect of the AuNRs. D) Tumor growth curves for mice treated with AuNRs and laser irradiation, compared with controls. Figure adapted, with permission, from reference .