Gold nanoparticle platforms as drug and biomacromolecule delivery systems

Abstract

Gold nanoparticles (AuNPs) are a suitable platform for development of efficient delivery systems. AuNPs can be easily synthesized, functionalized, and are biocompatible. The tunability of the AuNP monolayer allows for complete control of surface properties for targeting and stability/release using these nanocarriers. This review will discuss several delivery strategies utilizing AuNPs.

Figure 1

Particle size-dependent permeation of the tumor interstitial space. (A–C) Histological samples were obtained for 20, 60, and 100 nm particle sizes at 8 h postinjection (HPI). (D) ImageJ software was used to generate contrast-enhanced images for densitometry analysis. (E) Densitometry signal was quantified at 10 μm distances away from blood vessel centers 8 HPI and was normalized to the signal at 0–10 _m. Reprinted with permission from Ref. .

Figure 2

Nuclear targeting (A) by PEG-modified nanoparticles functionalized with a combination of CPPs (2% TAT and 2% Pntn) and 2% NLS. Nanoparticles are highlighted by red circles. The nuclear envelope with nuclear pores (arrows) is clearly shown in this image. The nucleus is denoted n, and the cytosol c. Unusual perinuclear membranous structures (B and C) that are highly loaded with nanoparticles are typically also observed under these conditions. Nuclear targeting is enhanced in comparison with experiments in the absence of CPPs (D). Scale bars are 200 nm. Reprinted with permission from Ref. .

Figure 3

(A) Photochemical reaction (365 nm) of Au_PCFU and delivery of payload to cell. (B) Cytotoxicity of different concentrations of Au_PCFU under uncaging and control conditions. The IC₅₀ value was 0.7 μM per particle, 11.9 μM per drug.

Figure 4

(A) Schematic illustration of GSH-mediated surface monolayer exchange reaction/payload release. (B) Fluorescence images of MEF cells displaying GSH-controlled release of the fluorophore after incubation with 0, 5, and 20 mM GSH-OEt.

Figure 5

(A) Schematic representation of AuNP and the nitroxide probe inclusion. (B) Plot of the ratio between the concentration of 2 partitioned in the monolayer and that of the free species (● 1.6 nm; ▼ 3.4 nm; ■ 5.3 nm) as a function of [HS-C8-TEG] bound to the gold. Reprinted with permission from Ref. .

Figure 6

(A) Structure of particles and guest compounds: Bodipy, TAF, and LAP, the number of encapsulated guests per particle (B) Cytotoxicity of AuNPZwit complexes measured by Alamar blue assay after 24 h incubation with MCF-7 cells. IC₅₀ of AuNP (NP), equivalent drugs (Drug), and free drugs are shown in table.

Figure 7

(A) Structure of the water-soluble Au NPs as a PDT drug delivery agent, Pc 4 structure (B) Fluorescence images of a tumor-bearing mouse after being injected with Au NP-Pc 4 conjugates in normal saline (0.9% NaCl, pH 7.2), (a) 1 min, (b) 30 min, and (c) 120 min after intravenous tail injection. Any bright signal is due to Pc 4 fluorescence. For comparison, a mouse that got only a Pc 4 formulation without the Au NP vector injected is shown in panel (d). No circulation of the drug in the body or into the tumor was detectable 2 h after injection without the Au NP as drug vector. Reprinted with permission from Ref. .