Gold nanorods (AuNRs) can be synthesised with different sizes but similar aspect ratios and therefore similar surface plasmon resonances (SPRs). Their strong optical absorbance governed by their SPRs facilitates their ability to be used as molecular-targeted contrast agents for photoacoustic (PA) imaging. The size of AuNRs has an effect on the PA conversion efficiency, melting threshold, and cytotoxicity, indicating that size can have a significant impact on overall biomedical efficacy. We investigated these factors for four different AuNRs (widths of 10, 25, 40 and 50 nm) all with SPRs of 815 ± 26 nm. A size-dependent linear relationship between fluence and PA amplitude was observed, along with particle melting. Reshaping was confirmed via transmission electron microscopy and spectrophotometry at a laser fluence of 11 ± 1.7 mJ cm−2, 20 ± 2.2 mJ cm−2, and 40 ± 2.6 mJ cm−2. Cytotoxicity was tested on lung cancer cells (A549) via a colourimetric assay at a maximum concentration of 3 × 1010 NP ml−1. Results demonstrate the 40 nm and 50 nm AuNRs produced the highest signal for equivalent particle numbers, but displayed the highest toxicity. Conversely, the 10 nm AuNRs were the most efficient photoacoustic converters, at equivalent total mass. This study demonstrates the importance of AuNR size and concentration on selection of AuNRs for their eventual clinical use.
Gold nanorods (AuNRs) have the potential to be used in photoacoustic (PA) imaging and plasmonic photothermal therapy (PPTT) due to their unique optical properties, biocompatibility, controlled synthesis, and tuneable surface plasmon resonances (SPRs). Conventionally, continuous-wave (CW) lasers are used in PPTT partly due to their small size and low cost. However, if pulsed-wave (PW) lasers could be used to destroy tissue then combined theranostic applications, such as PA-guided PPTT, would be possible using the same laser system and AuNRs. In this study, we present the effects of AuNR size on PA response, PW-PPTT efficacy, and PA imaging in a tissue-mimicking phantom, as a necessary step in the development of AuNRs towards clinical use. At equivalent NP/mL, the PA signal intensity scaled with AuNR size, indicating that overall mass has an effect on PA response, and reinforcing the importance of efficient tumour targeting. Under PW illumination, all AuNRs showed toxicity at a laser fluence below the maximum permissible exposure to skin, with a maximum of 80% cell-death exhibited by the smallest AuNRs, strengthening the feasibility of PW-PPTT. The theranostic potential of PW lasers combined with AuNRs has been demonstrated for application in the lung.
Lung cancer is a particularly difficult form of cancer to diagnose and treat, due largely to the inaccessibility of tumours and the limited available treatment options. The development of plasmonic gold nanoparticles has led to their potential use in a large range of disciplines, and they have shown promise for applications in this area. The ability to functionalise these nanoparticles to target to specific cancer types, when combined with minimally invasive therapies such as photothermal therapy, could improve long-term outcomes for lung cancer patients. Conventionally, continuous wave lasers are used to generate bulk heating enhanced by gold nanorods that have accumulated in the target region. However, there are potential negative side-effects of heat-induced cell death, such as the risk of damage to healthy tissue due to heat conducting to the surrounding environment, and the development of heat and drug resistance. In this study, the use of pulsed lasers for photothermal therapy was investigated and compared with continuous wave lasers for gold nanorods with a surface plasmon resonance at 850 nm, which were functionalised with anti-EGFR antibodies. Photothermal therapy was performed with both laser systems, on lung cancer cells (A549) in vitro populations incubated with untargeted and targeted nanorods. It was shown that the combination of pulse wave laser illumination of targeted nanoparticles produced a reduction of in the cell viability compared with control exposures, which demonstrates a possible application for minimally invasive therapies for lung cancer.
Plasmonic gold nanoparticles show potential for use in a range of cancer diagnostics and therapeutics, such as photoacoustic imaging (PAI) and plasmonic photothermal therapy (PPTT). Generally in PPTT, continuous wave (CW) lasers are used to destroy cancerous tissue. However, in order to add a diagnostic component through PAI, a pulsed wave (PW) laser is needed. If PPTT can be achieved using PW lasers then combined theranostic applications with the same laser system is possible. Additionally, AuNRs can be many different sizes but exhibit equivalent surface plasmon resonances, so the size may be significant in the efficacy of these modalities. We have demonstrated the potential for gold nanorods to be used for both PAI and PPTT. The Au10s displayed the highest photoacoustic signal amplitude and PPTT efficacy. A PW laser was shown to induce significant cell death to a lung cancer cell line with a fluence below the maximum permissible exposure, indicating the possibility for cancer theranostics with a PW laser.
1 January 2017 in Proceedings of Meetings on Acoustics
Plasmonic nanoparticles show great potential for molecular-targeted photoacoustic (PA) imaging. To maximise light absorption, the gold nanorods (AuNRs) are illuminated at their surface plasmon resonance (SPR), which for biomedical application is typically in the ’optical window’ of 700-900nm. For AuNRs, one of the main factors that determines the SPR is their aspect ratio. Since it is possible to have a similar aspect ratio, but different size of the particle the choice of particle could have a critical effect on a number of factors, such as, photoacoustic emissions, cell toxicity and therapeutic efficacy. For example, a particular sized AuNR may produce a higher PA response, for an equivalent laser fluence, but be more toxic to cell populations. In this study, the PA response of AuNRs with four different volumes but similar aspect ratios (∼4) are compared. A linear relationship between incident laser fluence and PA amplitude is shown and results indicate that AuNRs with larger volumes produce stronger PA emissions. In-vitro cell studies were performed on a lung cancer cell line to assess the cell toxicity of the different sized AuNRs via a colourmetric assay.