Nanomaterials, such as nanoparticles, nanorods, nanosphere, nanoshells, and nanostars, are very commonly used in biomedical imaging and cancer therapy. They make excellent drug carriers, imaging contrast agents, photothermal agents, photoacoustic agents, and radiation dose enhancers, among other applications. Recent advances in nanotechnology have led to the use of nanomaterials in many areas of functional imaging, cancer therapy, and synergistic combinational platforms. This review will systematically explore various applications of nanomaterials in biomedical imaging and cancer therapy. The medical imaging modalities include magnetic resonance imaging, computed tomography, positron emission tomography, single photon emission computerized tomography, optical imaging, ultrasound, and photoacoustic imaging. Various cancer therapeutic methods will also be included, including photothermal therapy, photodynamic therapy, chemotherapy, and immunotherapy. This review also covers theranostics, which use the same agent in diagnosis and therapy. This includes recent advances in multimodality imaging, image-guided therapy, and combination therapy. We found that the continuous advances of synthesis and design of novel nanomaterials will enhance the future development of medical imaging and cancer therapy. However, more resources should be available to examine side effects and cell toxicity when using nanomaterials in humans.

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Application of Nanomaterials in Biomedical Imaging and Cancer Therapy.

Photoacoustic (PA) imaging is an emerging imaging modality whereby pulsed laser illumination generates pressure transients that are detectable using conventional ultrasound. Plasmonic nanoparticles...

Engineering Plasmonic Nanoparticles for Enhanced Photoacoustic Imaging.

Lung cancer is one of the leading causes of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) causes around 80% to 90% of deaths. The lack of an early diagnosis and inefficiency in conventional therapies causes poor prognosis and overall survival of lung cancer patients. Recent progress in nanomedicine has encouraged the development of an alternative theranostics strategy using nanotechnology. The interesting physico-chemical properties in the nanoscale have generated immense advantages for nanoparticulate systems for the early detection and active delivery of drugs for a better theranostics strategy for lung cancer. This present review provides a detailed overview of the recent progress in the theranostics application of nanoparticles including liposomes, polymeric, metal and bio-nanoparticles. Further, we summarize the advantages and disadvantages of each approach considering the improvement for the lung cancer theranostics.

https://www.mdpi.com/2072-6694/11/5/597/pdf

Recent Progress in the Theranostics Application of Nanomedicine in Lung Cancer

Recent Advances in Molecular Imaging with Gold Nanoparticles.

The fabrication and development of nanomaterials for the treatment of prostate cancer have gained significant appraisal in recent years. Advancements in synthesis of organic and inorganic nanomaterials with charge, particle size, specified geometry, ligand attachment etc have resulted in greater biocompatibility and active targeting at cancer site. Despite all of the advances made over the years in discovering drugs, methods, and new biomarkers for cancer of the prostate (PCa), PCa remains one of the most troubling cancers among people. Early on, effective diagnosis is an essential part of treating prostate cancer. Prostate-specific antigen (PSA) or serum prostate-specific antigen is the best serum marker widely accessible for diagnosis of PCa. Numerous efforts have been made over the past decade to design new biosensor-based strategies for biomolecules detection and PSA miniaturization biomarkers. The growing nanotechnology is expected to have a significant effect in the immediate future on scientific research and healthcare. Nanotechnology is thus predicted to find a way to solve one of the most and long-standing problem, "early cancer detection". For early diagnosis of PCa biomarkers, different nanoparticles with different approaches have been used. In this review, we provide a brief description of the latest achievements and advances in the use of nanoparticles for PCa biomarker diagnosis.

https://www.mdpi.com/2079-4991/10/9/1696/pdf

Nanotreatment and Nanodiagnosis of Prostate Cancer: Recent Updates.

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.

Gold Nanorods for Light-Based Lung Cancer Theranostics.

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.

https://pubs.rsc.org/en/content/articlepdf/2019/NA/C8NA00389K

Optimising gold nanorods for photoacoustic imaging in vitro

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 93 % ± 13 % in the cell viability compared with control exposures, which demonstrates a possible application for minimally invasive therapies for lung cancer

Improving Plasmonic Photothermal Therapy of Lung Cancer Cells with Anti-EGFR Targeted Gold Nanorods.

Cancer is a complex disease with significant variability between cases, and as a result, is one of the leading causes of death worldwide. Lung cancer is a particularly difficult form of cancer to diagnose and treat, due largely to the inaccessibility of lung tumours and the limited available treatment options. There is a need for highly targeted, minimally invasive treatment options that facilitate the complete removal of cancer from a patient while minimising damage to non-malignant tissue. 

The development of plasmonic gold nanoparticles has lead to their potential use in a large range of disciplines, and in particular, they have shown great promise for application in biomedicine. Plasmonic gold nanoparticles possess many desirable characteristics, such as controllable size and shape during synthesis, the biocompatible and inert nature of gold, the potential functionalisation and surface modification prospects, and tunable surface plasmon resonances, that make them excellent candidates for biological use. These beneficial properties facilitate their use as contrast agents to further enhance existing light-based biomedical techniques, such as photoacoustic imaging and photothermal therapy, while possessing the ability to form new combined treatments.

In this thesis, gold nanorods - a subset of gold nanoparticles - will be investigated as a means to mediate photoacoustic imaging and photothermal therapy for combined lung cancer theranostics, while demonstrating their ability to improve current clinical practice. Since gold nanorods can be synthesised to be almost any size, and their aspect ratio governs their peak surface plasmon resonance, there may be an optimal sized AuNR for use in biomedical modalities that absorbs light at a particular wavelength. Four different sized gold nanorods (widths of 10, 25, 40, and 50 nm) with similar aspect ratios and therefore similar surface plasmon resonances (815 ± 26 nm) were considered for use in photoacoustic imaging. It was shown that the larger gold nanorods produced the highest photoacoustic amplitude at an equivalent number of nanoparticles, but were the most toxic, while the smallest gold nanorods were optimal at an equivalent total mass. The results indicate the importance for determining the dependence of total mass or number of nanoparticles on cellular targeting and uptake in vivo.

Gold nanorods can also be used as photoabsorbers for therapeutic modalities, such as photothermal therapy. Conventionally, continuous wave lasers are used to generate bulk heating in gold nanorods, that are situated in a target region, and the diseased tissue is destroyed via hyperthermia. 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 tothe surrounding environment, and the development of heat and drug resistance. Therefore, the use of pulsed lasers for photothermal therapy was investigated and compared with continuous wave lasers. It was shown that, for continuous wave lasers, a larger number of gold nanorods in the absorbing region resulted in increased cell death, whereas with pulsed lasers, the location of the gold nanorods, with respect to the cells, was the most important factor governing laser-induced toxicity. Furthermore, gold nanorods targeted to lung cancer EGFR receptors showed enhanced therapeutic efficacy under pulsed laser illumination.

Finally, the potential for gold nanorods to enhance endobronchial ultrasound - an existing clinical procedure for guiding lung cancer needle biopsies - was considered. This routine practice uses conventional B-mode ultrasound and a wide field of view to facilitate the locating of lymph nodes and guide the staging of lung cancer. This technique could be further improved with the use of gold nanorod mediated photoacoustic imaging with potentially minimal adaptation, since the underlying technology required to combine these modalities already exists. It was shown that inclusions of gold nanorods can be observed under pulsed laser illumination using imaging and transducer parameters comparable to that of endobronchial ultrasound. The potential for this promising new multimodality was demonstrated, with the aim of guiding future development. Overall, the work presented in this thesis provided valuable insights into the development of gold nanorods for biomedicine, and has demonstrated the potential for improving new and existing theranostic modalities.

Plasmonic Gold Nanoparticles: Combining Photoacoustic Imaging and Photothermal Therapy for New Cancer Treatments

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...

Oscar B. Knights

Papers

Gold Nanorods for Light-Based Lung Cancer Theranostics.

Optimising gold nanorods for photoacoustic imaging in vitro

Improving Plasmonic Photothermal Therapy of Lung Cancer Cells with Anti-EGFR Targeted Gold Nanorods.

Plasmonic Gold Nanoparticles: Combining Photoacoustic Imaging and Photothermal Therapy for New Cancer Treatments

Optimising gold nanorod size for maximum photoacoustic response while minimising cell toxicity