Recent advancements in photoacoustic (PA) imaging have leveraged reversibly photoswitchable chromophores, known for their dual absorbance states, to enhance imaging sensitivity through differential techniques. Yet, their deployment in tumor imaging has faced obstacles in achieving targeted delivery with high efficiency and specificity. Addressing this challenge, we introduce innovative protein assemblies, DrBphP-CBD, by genetically fusing a photosensory module from Deinococcus radiodurans bacterial phytochrome (DrBphP) with a collagen-binding domain (CBD). These protein assemblies form sub-100-nanometer structures composed of 24 DrBphP dimers and 12 CBD trimers, presenting 24 protein subunits. Their affinity for collagens, combined with impressive photoswitching contrast, markedly improves PA imaging precision. In various tumor models, intravenous administration of DrBphP-CBD has demonstrated enhanced tumor targeting and retention, augmenting contrast in PA imaging by minimizing background noise. This strategy underscores the clinical potential of DrBphP-CBD as PA contrast agents, propelling photoswitchable chromoproteins to the forefront of precise cancer diagnosis.

Recent advancements in cancer research have led to the generation of innovative nanomaterials for improved diagnostic and therapeutic strategies. Despite the proven potential of two-dimensional (2D) molybdenum disulfide (MoS2) as a versatile platform in biomedical applications, few review articles have focused on MoS2-based platforms for cancer theranostics. This review aims to fill this gap by providing a comprehensive overview of the latest developments in 2D MoS2 cancer theranostics and emerging strategies in this field. This review highlights the potential applications of 2D MoS2 in single-model imaging and therapy, including fluorescence imaging, photoacoustic imaging, photothermal therapy, and catalytic therapy. This review further classifies the potential of 2D MoS2 in multimodal imaging for diagnostic and synergistic theranostic platforms. In particular, this review underscores the progress of 2D MoS2 as an integrated drug delivery system, covering a broad spectrum of therapeutic strategies from chemotherapy and gene therapy to immunotherapy and photodynamic therapy. Finally, this review discusses the current challenges and future perspectives in meeting the diverse demands of advanced cancer diagnostic and theranostic applications.

Photoacoustics can provide a direct measurement of light absorption by microalgae depending on the photosynthesis pigment within them. In this study, we have performed photoacoustic flowmetry on living microalgae cells to measure their flow characteristics, which include flow speed, flow angle, flow direction, and, more importantly, the photoacoustic absorption spectrum, all by observing the photoacoustic Doppler power spectra during their flowing state. A supercontinuum pulsed laser with a high repetition frequency is used as the light source: through intensity modulation at a specified frequency, it can provide wavelength-selectable excitation of a photoacoustic signal centered around this frequency. Our approach can be useful to simultaneously measure the flow characteristics of microalgae and easily discriminate their different species with high accuracy in both static and dynamic states, thus facilitating the study of their cultivation and their role in our ecosystem.

Metal-modulated croconium dyes with multimodal-imaging and synergistic therapy in the tumor microenvironment have exhibited great potential in tumor theranostics. However, their unideal structure optimization always weakened the efficacy of near-infrared fluorescence-photoacoustic (NIRF/PA) imaging and photothermal therapy (PTT). Here, we screened croconium dye containing two indole groups with better NIRF/PA imaging and PTT in their family, linked to two morpholine rings, and obtained CR-736, as a lysosome-targeting and Fe3+-modulated agent. The established CR-736-Fe3+ nanoplatform was accurately delivered to the breast tumor site, released CR-736 and Fe3+ in the lower acidic lysosome microenvironment, and activated pH-responsive NIRF/PA/magnetic resonance imaging and PTT. Furthermore, ferroptosis generated hydroxyl free radicals and lipid peroxide by consuming GSH and H2O2 by dint of the accumulation of Fe3+ in tumor cells, which resulted in the inhibition of the expression of heat shock proteins and the concomitant recovery of PTT. The synergistic therapy of PTT, ferroptosis, and chemodynamics was further optimized to the maximal extent in tumor lysosome acidic microenvironment and proved both in vitro and a mouse tumor model. This study opens a new avenue in designing excellent and unique croconium-based nanoplatforms, synergizing multiple tumor theranostic methods, and further optimizing the theranostic effects in tumor microenvironment.

The current study explores the potential of ultrasound-assisted laser therapy (USaLT) to selectively destroy melanoma cells. The technology was tested on an ex vivo melanoma model, which was established by growing melanoma cells in chicken breast tissue. Ultrasound-only and laser-only treatments were used as control groups. USaLT was able to effectively destroy melanoma cells and selectively remove 66.41% of melanoma cells in the ex vivo tumor model when an ultrasound peak negative pressure of 2 MPa was concurrently applied with a laser fluence of 28 mJ/cm2 at 532 nm optical wavelength for 5 min. The therapeutic efficiency was further improved with the use of a higher laser fluence, and the treatment depth was improved to 3.5 mm with the use of 1,064 nm laser light at a fluence of 150 mJ/cm2. None of the laser-only and ultrasound-only treatments were able to remove any melanoma cells. The treatment outcome was validated with histological analyses and photoacoustic imaging. This study opens the possibility of USaLT for melanoma that is currently treated by laser therapy, but at a much lower laser fluence level, hence improving the safety potential of laser therapy.

Atrial fibrillation (A-fib) is the most common type of heart arrhythmia, typically treated with radiofrequency catheter ablation to isolate the heart from abnormal electrical signals. Monitoring the formation of ablation-induced lesions is crucial for preventing recurrences and complications arising from excessive or insufficient ablation. Existing imaging modalities lack real-time feedback, and their intraoperative usage is in its early stages. A critical need exists for an imaging-based lesion indexing (LSI) method that directly reflects tissue necrosis formation. Previous studies have indicated that spectroscopic photoacoustic (sPA) imaging can differentiate ablated tissues from their non-ablated counterparts based on PA spectrum variation. In this paper, we introduce a method for detecting ablation lesion boundaries using sPA imaging. This approach utilizes ablation LSI, which quantifies the ratio between the signal from ablated tissue and the total tissue signal. We enhance boundary detection accuracy by adapting a regression model-based compensation. Additionally, the method was cross-validated with clinically used intraoperative monitoring parameters. The proposed method was validated with ex vivo porcine cardiac tissues with necrotic lesions created by different ablation durations. The PA-measured lesion size was compared with gross pathology. Statistical analysis demonstrates a strong correlation (R > 0.90) between the PA-detected lesion size and gross pathology. The PA-detected lesion size also exhibits a moderate to strong correlation (R > 0.75) with local impedance changes recorded during procedures. These results suggest that the introduced PA imaging-based LSI has great potential to be incorporated into the clinical workflow, guiding ablation procedures intraoperatively.

Metal-organic frameworks (MOFs) have shown promise in enhancing the stability of biomolecules. Herein, biliverdin (BVD), a photoacoustic (PA) and fluorescent agent, was immobilized within the pores of NH2-MIL-101 (Fe) (FeMOFs) and on the surface of CuBTC crystallites (CuMOFs). MOFs were found to enhance the fluorescence emission and quench the PA intensity of biliverdin. Fluorescence and PA studies, in tandem with DFT simulations, demonstrated that the spectral interactions between MOFs and BVD resulted from interactions between biliverdin and the MOF pores and surfaces in addition to alterations in the HOMO-LUMO energy gap. The MOF internal structure of the MOF played a role in BVD loading, with the FeMOFs enabling greater BVD encapsulation, while CuMOF interactions with BVD primarily took place on the MOF surface. The role of these surface vs pore interactions in the release of biliverdin was explored. This study demonstrates that the effects of the MOF internal structure, surface interactions, and energy interactions should be taken into consideration for biomolecule loading in MOFs.

Photoacoustic imaging is an emerging modality with significant promise for biomedical applications such as neuroimaging, owing to its capability to capture large fields of view deep inside complex scattering tissue. However, widespread adoption of this technique has been hindered by a lack of suitable molecular reporters for this modality. In this work, we introduce chemigenetic labels and calcium sensors specifically tailored for photoacoustic imaging, using a combination of synthetic dyes and HaloTag-based self-labeling proteins. We rationally design and engineer far-red \"acoustogenic\" dyes, showing high photoacoustic turn-ons upon binding to HaloTag, and develop a suite of tunable calcium indicators based on these scaffolds. These first-generation photoacoustic reporters show excellent performance in tissue-mimicking phantoms, with the best variants outperforming existing sensors in terms of signal intensity, sensitivity, and photostability. We demonstrate the application of these ligands for labeling HaloTag-expressing neurons in mouse brain tissue, producing strong, specifically targeted photoacoustic signal, and provide a first example of in vivo labeling with these chemigenetic photoacoustic probes. Together, this work establishes a new approach for the design of photoacoustic reporters, paving the way toward deep tissue functional imaging.

UNASSIGNED: Photoacoustic imaging (PAI) is an emerging technology that holds high promise in a wide range of clinical applications, but standardized methods for system testing are lacking, impeding objective device performance evaluation, calibration, and inter-device comparisons. To address this shortfall, this tutorial offers readers structured guidance in developing tissue-mimicking phantoms for photoacoustic applications with potential extensions to certain acoustic and optical imaging applications.
UNASSIGNED: The tutorial review aims to summarize recommendations on phantom development for PAI applications to harmonize efforts in standardization and system calibration in the field.
UNASSIGNED: The International Photoacoustic Standardization Consortium has conducted a consensus exercise to define recommendations for the development of tissue-mimicking phantoms in PAI.
UNASSIGNED: Recommendations on phantom development are summarized in seven defined steps, expanding from (1) general understanding of the imaging modality, definition of (2) relevant terminology and parameters and (3) phantom purposes, recommendation of (4) basic material properties, (5) material characterization methods, and (6) phantom design to (7) reproducibility efforts.
UNASSIGNED: The tutorial offers a comprehensive framework for the development of tissue-mimicking phantoms in PAI to streamline efforts in system testing and push forward the advancement and translation of the technology.

Freehand optical ultrasound (OpUS) imaging is an emerging ultrasound imaging paradigm that uses an array of fibre-optic, photoacoustic ultrasound sources and a single fibre-optic ultrasound detector to perform ultrasound imaging without the need for electrical components in the probe head. Previous freehand OpUS devices have demonstrated capability for real-time, video-rate imaging of clinically relevant targets, but have been hampered by poor ultrasound penetration, significant imaging artefacts and low frame rates, and their designs limited their clinical applicability. In this work we present a novel freehand OpUS imaging platform, including a fully mobile and compact acquisition console and an improved probe design. The novel freehand OpUS probe presented utilises optical waveguides to shape the generated ultrasound fields for improved ultrasound penetration depths, an extended fibre-optic bundle to improve system versatility and an overall ruggedised design with protective elements to improve probe handling and protect the internal optical components. This probe is demonstrated with phantoms and the first multi-participant in vivo imaging study conducted with freehand OpUS imaging probes, this represents several significant steps towards the clinical translation of freehand OpUS imaging.