Gold nanotubes engineered for diagnosis and therapy

Pulsed near infrared light (shown in red) is shone onto a tumour (shown in white) that is encased in blood vessels. The tumour is imaged by multispectral optoacoustic tomography via the ultrasound emission (shown in blue) from the gold nanotubes. Image credit: Jing Claussen (iThera Medical, Germany)

Across a range of applications, the move from limited control of nanostructure toward the goal of eventual atomic precision is providing increased functional capabilities. Foresight President Paul Melnyk sends this example from Medgadget (written by Joshua Chen) of added benefits from controlling the length of gold nanotubes “Advancements In Gold Nanotechnology for Fighting Cancer“:

A study published in the scientific journal Advanced Functional Materials [abstract] describes for the first time the treatment of a human cancer in a mouse model using gold nanotubes. The group is able to control the length and tunable absorption of these gold nanoparticles in the near-infrared (NIR) region using a length-controlled synthesis method. They then apply a coating of poly(sodium 4-styrenesulfonate) (PSS) to allow the nanoparticles to maintain colloidal properties while maintaining low cytotoxicity. …

Further details are contained in a University of Leeds news release “Gold nanotubes launch a three-pronged attack on cancer cells“:

Study lead author Dr Sunjie Ye, who is based in both the School of Physics and Astronomy and the Leeds Institute for Biomedical and Clinical Sciences at the University of Leeds, said: “High recurrence rates of tumours after surgical removal remain a formidable challenge in cancer therapy. Chemo- or radiotherapy is often given following surgery to prevent this, but these treatments cause serious side effects.

Gold nanotubes – that is, gold nanoparticles with tubular structures that resemble tiny drinking straws – have the potential to enhance the efficacy of these conventional treatments by integrating diagnosis and therapy in one single system.”

The researchers say that a new technique to control the length of nanotubes underpins the research. By controlling the length, the researchers were able to produce gold nanotubes with the right dimensions to absorb a type of light called ‘near infrared’.

The study’s corresponding author Professor Steve Evans, from the School of Physics and Astronomy at the University of Leeds, said: “Human tissue is transparent for certain frequencies of light – in the red/infrared region. This is why parts of your hand appear red when a torch is shone through it.

“When the gold nanotubes travel through the body, if light of the right frequency is shone on them they absorb the light. This light energy is converted to heat, rather like the warmth generated by the Sun on skin. Using a pulsed laser beam, we were able to rapidly raise the temperature in the vicinity of the nanotubes so that it was high enough to destroy cancer cells.”

In cell-based studies, by adjusting the brightness of the laser pulse, the researchers say they were able to control whether the gold nanotubes were in cancer-destruction mode, or ready to image tumours.

In order to see the gold nanotubes in the body, the researchers used a new type of imaging technique called ‘multispectral optoacoustic tomography’ (MSOT) to detect the gold nanotubes in mice, in which gold nanotubes had been injected intravenously. It is the first biomedical application of gold nanotubes within a living organism. It was also shown that gold nanotubes were excreted from the body and therefore are unlikely to cause problems in terms of toxicity, an important consideration when developing nanoparticles for clinical use.

Study co-author Dr James McLaughlan, from the School of Electronic & Electrical Engineering at the University of Leeds, said: “This is the first demonstration of the production, and use for imaging and cancer therapy, of gold nanotubes that strongly absorb light within the ‘optical window’ of biological tissue.

“The nanotubes can be tumour-targeted and have a central ‘hollow’ core that can be loaded with a therapeutic payload. This combination of targeting and localised release of a therapeutic agent could, in this age of personalised medicine, be used to identify and treat cancer with minimal toxicity to patients.”

The use of gold nanotubes in imaging and other biomedical applications is currently progressing through trial stages towards early clinical studies.

Without the availability of a general technology for atomically precise manufacturing, these researchers combined several innovative approaches to obtain the properties they needed for these specific nanoparticles. For example, by reduction of silver nitrate under controlled conditions they were able to make silver seeds of 4 nm diameter. Upon adding these seeds to a growth solution containing more silver nitrate, ascorbic acid and PSS, they could generate hollow silver nanorods 50 nm in diameter. They could control nanorod length down to 300 nm by adjusting the seed amount and the growth temperature. The gold nanotubes were then formed by galvanic displacement of the silver nanorods. Coating the gold nanotubes with PSS gives the nanotubes colloidal stability and low toxicity to normal cells. The gold nanotubes had 6-nm thick walls, with distinct crystalline structures on the inside and outside walls to facilitate different functionalization for the inner and outer walls. Bringing these different approaches together, they have fabricated nanotubes with ideal properties for imaging, thermal killing of target cells, and drug delivery.
—James Lewis, PhD

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