Phase-locked µPIV analysis of flow dynamics in a simulated root canal with different laser-activated irrigations.

PURPOSE: To measure the dynamic characteristics of the flow field in a complex root canal model activated by two laser-activated irrigation (LAI) modalities at different activation energy outputs: photon-induced photoacoustic streaming (PIPS) and microshort pulse (MSP). METHODS: A phase-locked micro-scale Particle Image Velocimetry (µPIV) system was employed to characterise the temporal variations of LAI-induced velocity fields in the root canal following a single laser pulse. The wall shear stress (WSS) in the lateral root canal was subsequently estimated from the phase-averaged velocity fields. RESULTS: Both PIPS and MSP were able to generate the 'breath mode' of the irrigant current under all tested conditions. The transient irrigation flush in the root canal peaked at speeds close to 6 m/s. However, this intense flushing effect persisted for only about 2000 µs (or 3% of a single laser-pulse activation cycle). For MSP, the maximum WSS magnitude was approximately 3.08 Pa at an activation energy of E = 20 mJ/pulse, rising to 9.01 Pa at E = 50 mJ/pulse. In comparison, PIPS elevated the WSS to 10.63 Pa at E = 20 mJ/pulse. CONCLUSION: Elevating the activation energy can boost the peak flushing velocity and the maximum WSS, thereby enhancing irrigation efficiency. Given the same activation energy, PIPS outperforms MSP. Additionally, increasing the activation frequency may be an effective strategy to improve irrigation performance further.

Speckle Variance Photoacoustic Microscopy for Microhemodynamic Imaging.

Relying on the strong optical absorption of hemoglobin to pulsed laser energy, photoacoustic microscopy provides morphological and functional information on microvasculature label-freely. Here, we propose speckle variance photoacoustic microscopy (SV-PAM), which harnesses intrinsic imaging contrast from temporal-varied photoacoustic signals of moving red blood cells in blood vessels, for recovering three-dimension hemodynamic images down to capillary-level resolution within the microcirculatory tissue beds in vivo. Calculating the speckle variance of consecutive photoacoustic B-scan frames acquired at the same lateral position enables accurate identification of blood perfusion and occlusion, which provides interpretations of dynamic blood flow in the microvasculature, in addition to the microvascular anatomic structures. We demonstrate high-resolution hemodynamic imaging of vascular occlusion and reperfusion in the microvasculature of mice ears in vivo. The results suggest that our SV-PAM is potentially invaluable for biomedical hemodynamic investigations, for example, imaging ischemic stroke and hemorrhagic stroke.

Thermal-tagging photoacoustic remote sensing flowmetry.

Ultrasound coupling is one of the critical challenges for traditional photoacoustic (or optoacoustic) microscopy (PAM) techniques transferred to the clinical examination of chronic wounds and open tissues. A promising alternative potential solution for breaking the limitation of ultrasound coupling in PAM is photoacoustic remote sensing (PARS), which implements all-optical non-interferometric photoacoustic measurements. Functional imaging of PARS microscopy was demonstrated from the aspects of histopathology and oxygen metabolism, while its performance in hemodynamic quantification remains unexplored. In this Letter, we present an all-optical thermal-tagging flowmetry approach for PARS microscopy and demonstrate it with comprehensive mathematical modeling and ex vivo and in vivo experimental validations. Experimental results demonstrated that the detectable range of the blood flow rate was from 0 to 12 mm/s with a high accuracy (measurement error:±1.2%) at 10-kHz laser pulse repetition rate. The proposed all-optical thermal-tagging flowmetry offers an effective alternative approach for PARS microscopy realizing non-contact dye-free hemodynamic imaging.

Novel activated NIR-II fluorescence/Ratio photoacoustic probe for dual-modality accurate imaging of palladium ions overload in mouse liver.

Palladium contaminants can pose risks to human health and the natural environment. Once Pd2+ enters the body, it can bind with DNA, proteins, and other macromolecules, disrupting cellular processes and causing serious harm to health. Therefore, it becomes critical to develop simple, highly selective and precise methods for detecting Pd2+in vivo. Here, we have successfully developed the first activated second near-infrared region fluorescence (NIR-II FL) and ratio photoacoustic (PA) probe NYR-1 for dual-modal accurate detection of Pd2+ levels. NYR-1 is capable of rapidly (< 60 s) and sensitively detection of Pd2+ in solution, providing switched on NIR-II FL920 and ratio PA808/PA720 dual-mode signal change. More notably, the probe NYR-1 was successfully used for non-invasive imaging of Pd2+ overload in mouse liver by NIR-II FL/Ratio PA dual-modality imaging technology for the first time. Thus, this work opens up a promising dual-modal detection method for the precise detection of Pd2+ in organisms and in the environment.

Influence mechanism of the temporal duration of laser irradiation on photoacoustic technique: a review.

Significance: In the photoacoustic (PA) technique, the laser irradiation in the time domain (i.e., laser pulse duration) governs the characteristics of PA imaging-it plays a crucial role in the optical-acoustic interaction, the generation of PA signals, and the PA imaging performance. Aim: We aim to provide a comprehensive analysis of the impact of laser pulse duration on various aspects of PA imaging, encompassing the signal-to-noise ratio, the spatial resolution of PA imaging, the acoustic frequency spectrum of the acoustic wave, the initiation of specific physical phenomena, and the photothermal-PA (PT-PA) interaction/conversion. Approach: By surveying and reviewing the state-of-the-art investigations, we discuss the effects of laser pulse duration on the generation of PA signals in the context of biomedical PA imaging with respect to the aforementioned aspects. Results: First, we discuss the impact of laser pulse duration on the PA signal amplitude and its correlation with the lateral resolution of PA imaging. Subsequently, the relationship between the axial resolution of PA imaging and the laser pulse duration is analyzed with consideration of the acoustic frequency spectrum. Furthermore, we examine the manipulation of the pulse duration to trigger physical phenomena and its relevant applications. In addition, we elaborate on the tuning of the pulse duration to manipulate the conversion process and ratio from the PT to PA effect. Conclusions: We contribute to the understanding of the physical mechanisms governing pulse-width-dependent PA techniques. By gaining insight into the mechanism behind the influence of the laser pulse, we can trigger the pulse-with-dependent physical phenomena for specific PA applications, enhance PA imaging performance in biomedical imaging scenarios, and modulate PT-PA conversion by tuning the pulse duration precisely.

Photoacoustic microscopy for real-time monitoring of near-infrared optical absorbers inside biological tissue.

Significance: We developed a high-speed optical-resolution photoacoustic microscopy (OR-PAM) system using a high-repetition-rate supercontinuum (SC) light source and a two-axes Galvano scanner. The OR-PAM system enabled real-time imaging of optical absorbers inside biological tissues with excellent excitation wavelength tunability. Aim: In the near-infrared (NIR) wavelength range, high-speed OR-PAM faces limitations due to the lack of wavelength-tunable light sources. Our study aimed to enable high-speed OR-PAM imaging of various optical absorbers, including NIR contrast agents, and validate the performance of high-speed OR-PAM in the detection of circulating tumor cells (CTCs). Approach: A high-repetition nanosecond pulsed SC light source was used for OR-PAM. The excitation wavelength was adjusted by bandpass filtering of broadband light pulses produced by an SC light source. Phantom and in vivo experiments were performed to detect tumor cells stained with an NIR contrast agent within flowing blood samples. Results: The newly developed high-speed OR-PAM successfully detected stained cells both in the phantom and in vivo. The phantom experiment confirmed the correlation between the tumor cell detection rate and tumor cell concentration in the blood sample. Conclusions: The high-speed OR-PAM effectively detected stained tumor cells. Combining high-speed OR-PAM with molecular probes that stain tumor cells in vivo enables in vivo CTC detection.

Simultaneous photoacoustic and ultrasound imaging: A review.

Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that combines the advantages of optical and ultrasound imaging, enabling the generation of images with both optical resolution and acoustic penetration depth. By leveraging similar signal acquisition and processing methods, the integration of photoacoustic and ultrasound imaging has introduced a novel hybrid imaging modality suitable for clinical applications. Photoacoustic-ultrasound imaging allows for non-invasive, high-resolution, and deep-penetrating imaging, providing a wealth of image information. In recent years, with the deepening research and the expanding biomedical application scenarios of photoacoustic-ultrasound bimodal systems, the immense potential of photoacoustic-ultrasound bimodal imaging in basic research and clinical applications has been demonstrated, with some research achievements already commercialized. In this review, we introduce the principles, technical advantages, and biomedical applications of photoacoustic-ultrasound bimodal imaging techniques, specifically focusing on tomographic, microscopic, and endoscopic imaging modalities. Furthermore, we discuss the future directions of photoacoustic-ultrasound bimodal imaging technology.

Second Near-Infrared Macrophage-Biomimetic Nanoprobes for Photoacoustic Imaging of Neuroinflammation.

Neuroinflammation is a significant pathological event involving the neurodegenerative process associated with many neurological disorders. Diagnosis and treatment of neuroinflammation in its early stage are essential for the prevention and management of neurological diseases. Herein, we designed macrophage membrane-coated photoacoustic (PA) probes (MSINPs), with targeting specificities based on naturally existing target-ligand interactions for the early diagnosis of neuroinflammation. The second near-infrared dye, IR1061, was doped into silica as the core and was encapsulated with a macrophage membrane. In vitro as well as in vivo, the MSINPs could target inflammatory cells via the inflammation chemotactic effect. PA imaging was used to trace the MSINPs in a neuroinflammation mouse model and showed a great targeted effect of MSINPs in the prefrontal cortex. Therefore, the biomimetic nanoprobe prepared in this study offers a new strategy for PA molecular imaging of neuroinflammation, which can enhance our understanding of the evolution of neuroinflammation in specific brain regions.

Biosynthesis of CuTe Nanorods with Large Molar Extinction Coefficients for NIR-II Photoacoustic Imaging.

Photoacoustic imaging (PAI) in the second near-infrared region (NIR-II), due to deeper tissue penetration and a lower background interference, has attracted widespread concern. However, the development of NIR-II nanoprobes with a large molar extinction coefficient and a high photothermal conversion efficiency (PCE) for PAI and photothermal therapy (PTT) is still a big challenge. In this work, the NIR-II CuTe nanorods (NRs) with large molar extinction coefficients ((1.31 ± 0.01) × 108 cm-1·M-1 at 808 nm, (7.00 ± 0.38) × 107 cm-1·M-1 at 1064 nm) and high PCEs (70% at 808 nm, 48% at 1064 nm) were synthesized by living Staphylococcus aureus (S. aureus) cells as biosynthesis factories. Due to the strong light-absorbing and high photothermal conversion ability, the in vitro PA signals of CuTe NRs were about 6 times that of indocyanine green (ICG) in both NIR-I and NIR-II. In addition, CuTe NRs could effectively inhibit tumor growth through PTT. This work provides a new strategy for developing NIR-II probes with large molar extinction coefficients and high PCEs for NIR-II PAI and PTT.

A NIR-II Photoacoustic Probe for High Spatial Quantitative Imaging of Tumor Nitric Oxide in Vivo.

Nitric oxide (NO) exhibits both pro- and anti-tumor effects. Therefore, real-time in vivo imaging and quantification of tumor NO dynamics are essential for understanding the conflicting roles of NO played in pathophysiology. The current molecular probes, however, cannot provide high-resolution imaging in deep tissues, making them unsuitable for these purposes. Herein, we designed a photoacoustic probe with an absorption maximum beyond 1000 nm for high spatial quantitative imaging of in vivo tumor NO dynamics. The probe exhibits remarkable sensitivity, selective ratiometric response behavior, and good tumor-targeting abilities, facilitating ratiometric imaging of tumor NO throughout tumor progression in a micron-resolution level. Using the probe as the imaging agent, we successfully quantified NO dynamics in tumor, liver and kidney. We have pinpointed an essential concentration threshold of around 80 nmol/cm3 for NO, which plays a crucial role in the "double-edged-sword" function of NO in tumors. Furthermore, we revealed a reciprocal relationship between the NO concentration in tumors and that in the liver, providing initial insights into the possible NO-mediated communication between tumor and the liver. We believe that the probe will help resolve conflicting aspects of NO biology and guide the design of imaging agents for tumor diagnosis and anti-cancer drug screening.

Nanoscale engineering of gold nanostars for enhanced photoacoustic imaging.

Photoacoustic (PA) imaging is a diagnostic modality that combines the high contrast resolution of optical imaging with the high tissue penetration of ultrasound. While certain endogenous chromophores can be visualized via PA imaging, many diagnostic assessments require the administration of external probes. Anisotropic gold nanoparticles are particularly valued as contrast agents, since they produce strong PA signals and do not photobleach. However, the synthesis of anisotropic nanoparticles typically requires cytotoxic reagents, which can hinder their biological application. In this work, we developed new PA probes based on nanostar cores and polymeric shells. These AuNS were obtained through one-pot synthesis with biocompatible Good's buffers, and were subsequently functionalized with polyethylene glycol, chitosan or melanin, three coatings widely used in (pre)clinical research. Notably, the structural features of the nanostar cores strongly affected the PA signal. For instance, despite displaying similar sizes (i.e. 45 nm), AuNS obtained with MOPS buffer generated between 2 and 3-fold greater signal intensities in the region between 700 and 800 nm than nanostars obtained with HEPES and EPPS buffers, and up to 25-fold stronger signals than spherical gold nanoparticles. A point source analytical model demonstrated that AuNS synthesized with MOPS displayed greater absorption coefficients than the other particles, corroborating the stronger PA responses. Furthermore, the AuNS shell not only improved the biocompatibility of the nanoconstructs but also affected their performance, with melanin coating enhancing the signal more than 4-fold, due to its own PA capacity, as demonstrated by both in vitro and ex vivo imaging. Taken together, these results highlight the strengths of gold nanoconstructs as PA probes and offer insights into the design rules for the nanoengineering of new nanodiagnostic agents.

Video-rate endocavity photoacoustic/harmonic ultrasound imaging with miniaturized light delivery.

Significance: Endocavity ultrasound (US) imaging is a frequently employed diagnostic technique in gynecology and urology for the assessment of male and female genital diseases that present challenges for conventional transabdominal imaging. The integration of photoacoustic (PA) imaging with clinical US imaging has displayed promising outcomes in clinical research. Nonetheless, its application has been constrained due to size limitations, restricting it to spatially confined locations such as vaginal or rectal canals. Aim: This study presents the development of a video-rate (20 Hz) endocavity PA/harmonic US imaging (EPAUSI) system. Approach: The approach incorporates a commercially available endocavity US probe with a miniaturized laser delivery unit, comprised of a single large-core fiber and a line beamshaping engineered diffuser. The system facilitates real-time image display and subsequent processing, including angular energy density correction and spectral unmixing, in offline mode. Results: The spatial resolutions of the concurrently acquired PA and harmonic US images were measured at 318 µm and 291 µm in the radial direction, respectively, and 1.22 deg and 1.50 deg in the angular direction, respectively. Furthermore, the system demonstrated its capability in multispectral PA imaging by successfully distinguishing two clinical dyes in a tissue-mimicking phantom. Its rapid temporal resolution enabled the capture of kinetic dye perfusion into an ex vivo porcine ovary through the depth of porcine uterine tissue. EPAUSI proved its clinical viability by detecting pulsating hemodynamics in the male rat's prostate in vivo and accurately classifying human blood vessels into arteries and veins based on sO2 measurements. Conclusions: Our proposed EPAUSI system holds the potential to unveil previously overlooked indicators of vascular alterations in genital cancers or endometriosis, addressing pressing requirements in the fields of gynecology and urology.

Hybrid spherical array for combined volumetric optoacoustic and B-mode ultrasound imaging.

Optoacoustic (OA) imaging has achieved tremendous progress with state-of-the-art systems providing excellent functional and molecular contrast, centimeter scale penetration into living tissues, and ultrafast imaging performance, making it highly suitable for handheld imaging in the clinics. OA can greatly benefit from efficient integration with ultrasound (US) imaging, which remains the routine method in bedside clinical diagnostics. However, such integration has not been straightforward since the two modalities typically involve different image acquisition strategies. Here, we present a new, to our knowledge, hybrid optoacoustic ultrasound (OPUS) imaging approach employing a spherical array with dedicated segments for each modality to enable volumetric OA imaging merged with conventional B-mode US. The system performance is subsequently showcased in healthy human subjects. The new OPUS approach hence represents an important step toward establishing OA in point-of-care diagnostic settings.

Wearable photoacoustic watch for humans.

Longitudinal detection of hemodynamic changes based on wearable devices is imperative for monitoring human healthcare. Photoacoustic effect is extremely sensitive to variations in hemoglobin. Therefore, wearable photoacoustic devices are apt to monitor human healthcare via the observation of hemodynamics. However, the bulky system and difficulties in miniaturizing and optimizing the imaging interface restrict the development of wearable photoacoustic devices for human use. In this study, we developed a wearable photoacoustic watch with a fully integrated system in a backpack that has a size of 450 mm × 300 mm × 200 mm and an affordable weight of 7 kg for an adult to wear. The watch has a size of 43 mm × 30 mm × 24 mm, weighs 40 g, and features a lateral resolution of 8.7 µm, a field of view (FOV) of 3 mm in diameter, and a motorized adjustable focus for optimizing the imaging plane for different individuals. We recruited volunteers to wear the watch and the backpack and performed in vivo imaging of the vasculatures inside human wrists under the conditions of walking and human cuff occlusion to observe hemodynamic variations during different physiological states. The results suggest that the focus shifting capability of the watch makes it suitable for different individuals, and the compact and stable design of the entire system allows free movements of humans.

Fused Azulenyl Squaraine Derivatives Improve Phototheranostics in the Second Near-Infrared Window by Concentrating Excited State Energy on Non-Radiative Decay Pathways.

The second near-infrared (NIR-II) theranostics offer new opportunities for precise disease phototheranostic due to the enhanced tissue penetration and higher maximum permissible exposure of NIR-II light. However, traditional regimens lacking effective NIR-II absorption and uncontrollable excited-state energy decay pathways often result in insufficient theranostic outcomes. Herein a phototheranostic nano-agent (PS-1 NPs) based on azulenyl squaraine derivatives with a strong NIR-II absorption band centered at 1092 nm is reported, allowing almost all absorbed excitation energy to dissipate through non-radiative decay pathways, leading to high photothermal conversion efficiency (90.98 %) and strong photoacoustic response. Both in vitro and in vivo photoacoustic/photothermal therapy results demonstrate enhanced deep tissue cancer theranostic performance of PS-1 NPs. Even in the 5 mm deep-seated tumor model, PS-1 NPs demonstrated a satisfactory anti-tumor effect in photoacoustic imaging-guided photothermal therapy. Moreover, for the human extracted tooth root canal infection model, the synergistic outcomes of the photothermal effect of PS-1 NPs and 0.5 % NaClO solution resulted in therapeutic efficacy comparable to the clinical gold standard irrigation agent 5.25 % NaClO, opening up possibilities for the expansion of NIR-II theranostic agents in oral medicine.

Optical ultrasound sensors for photoacoustic imaging: a review.

Significance: Photoacoustic (PA) imaging is an emerging biomedical imaging modality that can map optical absorption contrast in biological tissues by detecting ultrasound signal. Piezoelectric transducers are commonly used in PA imaging to detect the ultrasound signals. However, piezoelectric transducers suffer from low sensitivity when the dimensions are reduced and are easily influenced by electromagnetic interference. To avoid these limitations, various optical ultrasound sensors have been developed and shown their great potential in PA imaging. Aim: Our study aims to summarize recent progress in optical ultrasound sensor technologies and their applications in PA imaging. Approach: The commonly used optical ultrasound sensing techniques and their applications in PA systems are reviewed. The technical advances of different optical ultrasound sensors are summarized. Results: Optical ultrasound sensors can provide wide bandwidth and improved sensitivity with miniatured size, which enables their applications in PA imaging. Conclusions: The optical ultrasound sensors are promising transducers in PA imaging to provide higher-resolution images and can be used in new applications with their unique advantages.

Acoustic hologram-induced virtual in vivo enhanced waveguide (AH-VIEW).

Optical imaging and phototherapy in deep tissues face notable challenges due to light scattering. We use encoded acoustic holograms to generate three-dimensional acoustic fields within the target medium, enabling instantaneous and robust modulation of the volumetric refractive index, thereby noninvasively controlling the trajectory of light. Through this approach, we achieved a remarkable 24.3% increase in tissue heating rate in vitro photothermal effect tests on porcine skin. In vivo photoacoustic imaging of mouse brain vasculature exhibits an improved signal-to-noise ratio through the intact scalp and skull. These findings demonstrate that our strategy can effectively suppress light scattering in complex biological tissues by inducing low-angle scattering, achieving an effective depth reaching the millimeter scale. The versatility of this strategy extends its potential applications to neuroscience, lithography, and additive manufacturing.

Intravital photoacoustic brain stimulation with high-precision.

Significance: Neural regulation at high precision vitally contributes to propelling fundamental understanding in the field of neuroscience and providing innovative clinical treatment options. Recently, photoacoustic brain stimulation has emerged as a cutting-edge method for precise neuromodulation and shows great potential for clinical application. Aim: The goal of this perspective is to outline the advancements in photoacoustic brain stimulation in recent years. And, we also provide an outlook delineating several prospective paths through which this burgeoning approach may be substantively refined for augmented capability and wider implementations. Approach: First, the mechanisms of photoacoustic generation as well as the potential mechanisms of photoacoustic brain stimulation are provided and discussed. Then, the state-of-the-art achievements corresponding to this technology are reviewed. Finally, future directions for photoacoustic technology in neuromodulation are provided. Results: Intensive research endeavors have prompted substantial advancements in photoacoustic brain stimulation, illuminating the unique advantages of this modality for noninvasive and high-precision neuromodulation via a nongenetic way. It is envisaged that further technology optimization and randomized prospective clinical trials will enable a wide acceptance of photoacoustic brain stimulation in clinical practice. Conclusions: The innovative practice of photoacoustic technology serves as a multifaceted neuromodulation approach, possessing noninvasive, high-accuracy, and nongenetic characteristics. It has a great potential that could considerably enhance not only the fundamental underpinnings of neuroscience research but also its practical implementations in a clinical setting.

Nanofibers of N,N,N-trimethyl chitosan capped bimetallic nanoparticles: Preparation, characterization, wound dressing and in vivo treatment of MDR microbial infection and tracking by optical and photoacoustic imaging.

Recent advancements in wound care have led to the development of interactive wound dressings utilizing nanotechnology, aimed at enhancing healing and combating bacterial infections while adhering to established protocols. Our novel wound dressings consist of N,N,N-trimethyl chitosan capped gold­silver nanoparticles (Au-Ag-TMC-NPs), with a mean size of 108.3 ± 8.4 nm and a zeta potential of +54.4 ± 1.8 mV. These optimized nanoparticles exhibit potent antibacterial and antifungal properties, with minimum inhibitory concentrations ranging from 0.390 µg ml-1 to 3.125 µg ml-1 and also exhibited promising zones of inhibition against multi-drug resistant strains of S. aureus, E. coli, P. aeruginosa, and C. albicans. Microbial transmission electron microscopy reveals substantial damage to cell walls and DNA condensation post-treatment. Furthermore, the nanoparticles demonstrate remarkable inhibition of microbial efflux pumps and are non-hemolytic in human blood. Incorporated into polyvinyl alcohol/chitosan nanofibers, they form Au-Ag-TMC-NPs-NFs with diameters of 100-350 nm, facilitating efficient antimicrobial wound dressing. In vivo studies on MDR microbial-infected wounds in mice showed 99.34 % wound healing rate within 12 days, corroborated by analyses of wound marker protein expression levels and advanced imaging techniques such as ultrasound/photoacoustic imaging, providing real-time visualization and blood flow assessment for a comprehensive understanding of the dynamic wound healing processes.

Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases.

Pancreatic cancer is highly lethal. New diagnostic and treatment modalities are desperately needed. We report here that an expanded porphyrin, cyclo[8]pyrrole (CP), with a high extinction coefficient (89.16 L/g·cm) within the second near-infrared window (NIR-II), may be formulated with an αvß3-specific targeting peptide, cyclic-Arg-Gly-Asp (cRGD), to form cRGD-CP nanoparticles (cRGD-CPNPs) with promising NIR-II photothermal (PT) therapeutic and photoacoustic (PA) imaging properties. Studies with a ring-array PA tomography system, coupled with analysis of control nanoparticles lacking a targeting element (CPNPs), revealed that cRGD conjugation promoted the delivery of the NPs through abnormal vessels around the tumor to the solid tumor core. This proved true in both subcutaneous and orthotopic pancreatic tumor mice models, as confirmed by immunofluorescent studies. In combination with NIR-II laser photoirradiation, the cRGD-CPNPs provided near-baseline tumor growth inhibition through PTT both in vitro and in vivo. Notably, the combination of the present cRGD-CPNPs and photoirradiation was found to inhibit intra-abdominal metastases in an orthotopic pancreatic tumor mouse model. The cRGD-CPNPs also displayed good biosafety profiles, as inferred from PA tomography, blood analyses, and H&E staining. They thus appear promising for use in combined PA imaging and PT therapeutic treatment of pancreatic cancer.