Nanotechnology-based cancer treatment approaches potentially provide localized, targeted therapies that aim to enhance efficacy, reduce side effects, and improve patient quality of life. Gold-nanoparticle-mediated hyperthermia shows particular promise in animal studies, and early clinical testing is currently underway. In this article, the rapidly evolving field of gold nanoparticle thermal therapy is reviewed, highlighting recent literature and describing current challenges to clinical translation of the technology.

A New Era for Cancer Treatment: Gold‐Nanoparticle‐Mediated Thermal Therapies

Triggerable drug delivery systems enable on-demand controlled release profiles that may enhance therapeutic effectiveness and reduce systemic toxicity. Recently, a number of new materials have been developed that exhibit sensitivity to visible light, near-infrared (NIR) light, ultrasound, or magnetic fields. This responsiveness can be triggered remotely to provide flexible control of dose magnitude and timing. Here we review triggerable materials that range in scale from nano to macro, and are activated by a range of stimuli.

Remotely triggerable drug delivery systems.

Nanomaterials that interact with light provide a unique opportunity for applications in biophotonic nanomedicine. Image-guided therapies could be designed based on multifunctional nanoparticles (NPs). Such NPs have a strong and tunable surface plasmon resonance absorption in the near-infrared region and can be detected using multiple imaging modalities (magnetic resonance imaging, nuclear imaging, and photoacoustic imaging). These novel nanostructures, once introduced, are expected to home in on solid tumors either via a passive targeting mechanism (i.e., the enhanced permeability and retention effect) or via an active targeting mechanism facilitated by ligands bound to their surfaces. Once the NPs reach their target tissue, their activity can then be turned on using an external stimulus. For example, photothermal conducting NPs primarily act by converting light energy into heat. As a result, the temperature in the treatment volume is elevated above the thermal damage threshold, which kills the cells. Thi...

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Cancer theranostics with near-infrared light-activatable multimodal nanoparticles.

Photochemical mechanisms of light-triggered release from nanocarriers

The temporal and spatial control over the delivery of materials such as siRNA into cells remains a significant technical challenge. We demonstrate the pulsed near-infrared (NIR) laser-dependent release of siRNA from coated 40 nm gold nanoshells. Tat-lipid coating mediates the cellular uptake of the nanomaterial at picomolar concentration, while spatiotemporal silencing of a reporter gene (green fluorescence protein) was studied using photomasking. The NIR laser-induced release of siRNA from the nanoshells is found to be power- and time-dependent, through surface-linker bond cleavage, while the escape of the siRNA from endosomes occurs above a critical pulse energy attributed to local heating and cavitation. NIR laser-controlled drug release from functional nanomaterials should facilitate more sophisticated developmental biology and therapeutic studies.

Laser-Activated Gene Silencing via Gold Nanoshell−siRNA Conjugates

A simplified synthesis of hollow gold nanoshells 20-50 nm in diameter via the well-established templated galvanic replacement reaction of silver for gold is presented. The surface plasmon resonance absorbance of the nanoshells is tuned using basic colloid chemistry to control the size of the silver templates. The gold nanoshells have an aqueous core and are varied in size and shell thickness depending on the silver/gold reagent ratios. The template replacement chemistry is rapid, highly scalable, uses minimal amounts of toxic reagents, and in many cases is a true one-pot synthesis. The smallest nanoshells (20-nm diameter, 7-nm wall thickness) reach the highest temperature on irradiation with femtosecond light pulses in the near infrared and anneal to form spherical nanoparticles fastest, even though their plasmon resonance does not overlap as well as the larger nanoshells (50-nm diameter, 7-nm wall thickness) with 800-nm wavelength excitation.

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Brian G. Prevo

Papers

Scalable routes to gold nanoshells with tunable sizes and response to near-infrared pulsed-laser irradiation.