Photoacoustic imaging using exogenous contrast agents has emerged as a hybrid technique that enables the deep imaging of optical properties of tissues with high spatial resolution. The power of this imaging technique can be greatly enhanced by the use of contrast agents that absorb at near-infrared wavelengths and whose optical properties can be modulated in response to the local environment. We have designed contrast agents consisting of gold nanoparticles coated with anisotropic silica nanoshells. The tunable aggregation of these janus particles in cell culture media resulted in a dramatic amplification of photoacoustic signals in the near-infrared region. We also demonstrated imaging using these contrast agents in mammalian cells, including macrophages and breast cancer cells as well as in vivo. The ability to modulate janus particle aggregation in response to a range of stimuli in combination with the high resolution and deep penetration of multiwavelength photoacoustic imaging are attractive for a broad range of applications in diagnostic imaging and theranostics.

A minimally invasive method to detect lymph node metastases using glycol-chitosan-coated gold nanoparticles and ultrasound-guided photoacoustic imaging.

Lymph node mapping is important in cancer immunotherapy because the morphology of lymph nodes is one of the crucial evaluation criteria of immune responses. We developed new theragnostic glycol-chitosan-coated gold nanoparticles (GC-AuNPs), which highlighted lymph nodes in ultrasound-guided photoacoustic (US/PA) imaging. Moreover, the ovalbumin epitope was conjugated GC-AuNPs (OVA-GC-AuNPs) for delivering tumor antigen to lymph node resident macrophage. In vitro studies proved the vigorous endocytosis activity of J774A.1 macrophage and consequent strong photoacoustic signals from them. The macrophages also presented a tumor antigen when OVA-GC-AuNPs were used for cellular uptake. After the lingual injection of GC-AuNPs into healthy mice, cervical lymph nodes were visible in a US/PA imaging system with high contrast. Three-dimensional analysis of lymph nodes revealed that the accumulation of GC-AuNPs in the lymph node increased as the post-injection time passed. Histological analysis showed GC-AuNPs or OVA-GC-AuNPs located in subcapsular and medullar sinuses where macrophages are abundant. Our new theragnostic GC-AuNPs present a superior performance in US/PA imaging of lymph nodes without targeting moieties or complex surface modification. Simultaneously, GC-AuNPs were able to deliver tumor antigens to cause macrophages to present the OVA epitope at targeted lymph nodes, which would be valuable for cancer immunotherapy.

Photoacoustic (PA) imaging (PAI) is an emerging imaging modality that takes advantage of the optical absorption properties of tissue to generate high-resolution in vivo images of anatomy and exogenous chromophores.¹ PAI works through the PA effect: pulsed light delivered to a sample is absorbed, thereby causing thermoelastic expansion and generating acoustic pressure waves.^2,3 These acoustic waves are detected by an ultrasound transducer and reconstructed to form an image. In the near-infrared (NIR) window, oxyhemoglobin and deoxyhemoglobin have relatively high optical absorption coefficients compared to other endogenous chromophores, enabling PAI to detect and highlight blood-rich tissues in vivo with a spatial resolution comparable to ultrasound imaging.^{4 – 8} The high contrast and sensitivity of these blood-rich tissues are responsible for PAI’s suitability as a functional and anatomical imaging modality. Additionally, PA contrast agents are designed with optical absorption properties that can be exploited with multispectral (i.e., multiwavelength) PAI.^{9 – 14}

Photothermal therapy (PTT) is a type of cancer treatment capable of damaging tumors using laser irradiation. This procedure can be a promising approach to complement current cancer therapies, due in part to its minimal invasiveness. One of the challenges of photothermal therapy is the potential collateral damage to the surrounding healthy tissue, as well as excessive temperature increase in the target tumor region that can cause tissue carbonization and evaporation. With the aim of increasing the performance of photothermal therapy in damaging targeted tumor while keeping healthy nearby tissue unaffected, this research proposes the use of a feedback control system that considers the cumulative thermal damage to both types of tissue. Two separate control algorithms (fuzzy logic and PI) were designed and tested in silico using simulations made in MATLAB® and Python. Results showed that both controllers successfully accomplished the proposed goals. Therefore, the feasibility of using these automated systems to improve the efficacy and safety of PTT was demonstrated.