Gold nanoparticles in delivery applications☆
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).
References (78)
- et al.
Nanotechnologies for biomolecular detection and medical diagnostics
Curr. Opin. Chem. Biol.
(2006) - et al.
Coating gold nanoparticles with peptide molecules via a peptide elongation approach
Colloids Surf., B Biointerfaces
(2003) - et al.
PEGylated nanoparticles for biological and pharmaceutical applications
Adv. Drug Deliv. Rev.
(2003) Glutathione: an overview of biosynthesis and modulation
Chem.-Biol. Interact.
(1998)Glutathione and its role in cellular functions
Free Radic. Biol. Med.
(1999)- et al.
Redox state of glutathione in human plasma
Free Radic. Biol. Med.
(2000) - et al.
Glutathione measurement in human plasma evaluation of sample collection, storage and derivatization conditions for analysis of dansyl derivatives by HPLC
Clin. Chim. Acta
(1998) - et al.
Drug delivery strategy utilizing conjugation via reversible disulfide linkages: role and site of cellular reducing activities
Adv. Drug Deliv. Rev.
(2003) - et al.
Stability of bioreductive drug delivery systems containing melphalan is influenced by conformational constraint and electronic properties of substituents
Bioorg. Med. Chem. Lett.
(2000) - et al.
Thiolated chitosans: development and in vitro evaluation of a mucoadhesive, permeation enhancing oral drug delivery system
J. Control. Release
(2004)
Barriers to nonviral gene delivery
J. Pharm. Sci.
Au nanoparticles target cancer
Nano Today
Nanoparticle and targeted systems for cancer therapy
Adv. Drug Deliver. Rev.
Nanoparticles in cancer therapy and diagnosis
Adv. Drug Deliv. Rev.
Control of tumour vascular permeability
Adv. Drug Deliv. Rev.
Cancer nanotechnology: opportunities and challenges
Nat. Rev., Cancer
Targeted charge-reversal nanoparticles for nuclear drug delivery
Angew. Chem., Int. Ed.
Acid- and salt-triggered multifunctional poly(propylene imine) dendrimer as a prospective drug delivery system
Biomacromolecules
The vesosome — a multicompartment drug delivery vehicle
Curr. Med. Chem.
Targeted delivery of amphotericin B to cells by using functionalized carbon nanotubes
Angew. Chem., Int. Ed.
Multifunctional nanorods for gene delivery
Nat. Mater.
Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery
Drug Deliv.
Colloidal gold nanoparticles: a novel nanoparticle platform for developing multifunctional tumor-targeted drug delivery vectors
Drug Dev. Res.
Glutathione-mediated delivery and release using monolayer protected nanoparticle carriers
J. Am. Chem. Soc.
Water-soluble nitric oxide-releasing gold nanoparticles
Langmuir
Light-regulated release of DNA and its delivery to nuclei by means of photolabile gold nanoparticles
Angew. Chem., Int. Ed.
Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity
Small
Laser-induced release of encapsulated materials inside living cells
Angew. Chem. Int. Ed.
Nanostructures in biodiagnostics
Chem. Rev.
Large clusters and colloids — metals in the embryonic state
Chem. Rev.
Synthesis of thiol-derivatized gold nanoparticles in a 2-phase liquid–liquid system
J. Chem. Soc., Chem. Commun.
Monolayer protected cluster molecules
Acc. Chem. Res.
Preparation and characterization of Au colloid monolayers
Anal. Chem.
Controlled nucleation for regulation of particle-size in monodisperse gold suspensions
Nature Phys. Sci.
A study of the nucleation and growth processes in the synthesis of colloidal gold, discuss
Faraday Soc.
Ligand density effect on biorecognition by PEGylated gold nanoparticles: regulated interaction of RCA(120) lectin with lactose installed to the distal end of tethered PEG strands on gold surface
Biomacromolecules
Quantitative and reversible lectin-induced association of gold nanoparticles modified with alpha-lactosyl-omega-mercapto-poly(ethylene glycol)
J. Am. Chem. Soc.
Preparation of functionally PEGylated gold nanoparticles with narrow distribution through autoreduction of auric cation by alpha-biotinyl-PEG-block-[poly(2-(N,N-dimethylamino)ethyl methacrylate)]
Langmuir
Synthesis of zerovalent nanophase metal particles stabilized with poly(ethylene glycol)
Langmuir
Cited by (2382)
A comprehensive review on nanofluids: Synthesis, cutting-edge applications, and future prospects
2024, International Journal of ThermofluidsA review of hyaluronic acid-based therapeutics for the treatment and management of arthritis
2024, International Journal of Biological MacromoleculesPhoto-triggered multifunctional gold-based hybrid nanoflowers promote infectious skin regeneration
2024, Chemical Engineering JournalThe application of nanomaterials in designing promising diagnostic, preservation, and therapeutic strategies in combating male infertility: A review
2024, Journal of Drug Delivery Science and Technology
- ☆
This review is part of the Advanced Drug Delivery Reviews theme issue on “Inorganic Nanoparticles in Drug Delivery”.