Elsevier

Advanced Drug Delivery Reviews

Volume 60, Issue 11, 17 August 2008, Pages 1307-1315
Advanced Drug Delivery Reviews

Gold nanoparticles in delivery applications

https://doi.org/10.1016/j.addr.2008.03.016Get rights and content

Abstract

Gold nanoparticles (AuNPs) provide non-toxic carriers for drug and gene delivery applications. With these systems, the gold core imparts stability to the assembly, while the monolayer allows tuning of surface properties such as charge and hydrophobicity. An additional attractive feature of AuNPs is their interaction with thiols, providing an effective and selective means of controlled intracellular release.

Introduction

Nanocarriers have provided a novel platform for target-specific delivery of therapeutic agents [1]. Over the past decade, several delivery vehicles have been designed based on different nanomaterials, such as polymers [2], dendrimers [3], liposomes [4], nanotubes [5], and nanorods [6]. Gold nanoparticles (GNPs) have recently emerged as an attractive candidate for delivery of various payloads into their targets [7], [8]. The payloads could be small drug molecules or large biomolecules, like proteins, DNA, or RNA (vide post). Efficient release of these therapeutic agents is a prerequisite for effective therapy. The release could be triggered by internal (e.g. glutathione (GSH) [9], or pH [10]) or external (e.g. light [11]) stimuli. Significantly the internal stimuli operate in a biologically control manner, whereas the external stimuli provide spatio-temporal control over the release.

Gold nanoparticles exploit their unique chemical and physical properties for transporting and unloading the pharmaceuticals. First, the gold core is essentially inert and non-toxic [12]. A second advantage is their ease of synthesis; monodisperse nanoparticles can be formed with core sizes ranging from 1 nm to 150 nm (Table 1). Further versatility is imparted by their ready functionalization, generally through thiol linkages (vide post). Moreover, their photophysical properties could trigger drug release at remote place [13].

Several reviews describing nanoparticle–biomacromolecule interactions have recently been published, generally focusing on biosensing [14] and diagnostic [15] applications. This review will focus on drug, gene, and protein delivery using GNPs (Fig. 1).

Section snippets

Synthesis of gold nanoparticles

Significant efforts have been devoted over the past forty years to the fabrication of GNPs with monodispersity and controlled size. GNPs with varying core sizes are prepared by the reduction of gold salts in the presence of appropriate stabilizing agents that prevent particle agglomeration. Some common synthetic methods of core–shell GNPs are summarized in Table 1.

Several research groups have fabricated delivery systems based on GNPs bearing functional moieties, which are anchored with

Drug delivery using gold nanoparticles

Drug delivery systems (DDSs) provide positive attributes to a ‘free’ drug by improving solubility, in vivo stability, and biodistribution. They can also alter unfavorable pharmacokinetics of some ‘free’ drugs. Moreover, huge loading of pharmaceuticals on DDSs can render ‘drug reservoirs’ for controlled and sustained release to maintain the drug level within therapeutic window. For example, a gold nanoparticle with 2 nm core diameter could be, in principle, conjugated with ∼ 100 molecules to

Gold nanoparticles for delivery of biomolecules

Gold nanoparticles are capable of delivering large biomolecules, without restricting themselves as carriers of only small molecular drugs. Tunable size and functionality make them a useful scaffold for efficient recognition and delivery of biomolecules. They have shown the success in delivery of peptides, proteins, or nucleic acids like DNA or RNA.

Photothermal effect of gold nanoparticles in therapy

In addition to the surface chemistry of GNPs, their physical properties could be exploited for delivery applications [67]. GNPs cause local heating when they are irradiated with light in the “water window” (800 nm–1200 nm). El-Sayed et al. have recently reported about potential use of GNPs in photothermal destruction of tumors [68]. Citrate-stabilized GNPs (core d = 30 nm) were coated with anti-EGFR (epidermal growth factor receptor) to target HSC3 cancer cells (human oral squamous cell

Gold nanoparticle targeting in vivo

For in vivo applications, the goal of nanocarriers is to arrive at the diseased tissues after administration into circulatory system. Two approaches have been developed for targeting — namely ‘passive’ and ‘active’ targeting (Fig. 10) [70], [71]. ‘Passive’ targeting depends on homing of the vectors in unhealthy tissues due to extravasation through leaky (gaps ∼ 600 nm) blood vessel. An important aspect of carrier systems in the 5–10 nm scale is their ability to take advantage of the enhanced

Conclusions

Gold nanoparticles have emerged as a promising scaffold for drug and gene delivery that provide a useful complement to more traditional delivery vehicles. Their combination of low inherent toxicity, high surface area and tunable stability provides them with unique attributes that should enable new delivery strategies. The key issue that needs to be addressed is the engineering of the particle surface for optimizing properties such as bioavailability and non-immunogenicity.

Acknowledgements

This research was supported by the NIH (GM077173) and the NSF Center for Hierarchical Manufacturing at the University of Massachusetts (NSEC, DMI-0531171).

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    This review is part of the Advanced Drug Delivery Reviews theme issue on “Inorganic Nanoparticles in Drug Delivery”.

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