Photoacoustic Imaging Performance Research Articles

Enhanced dual-mode imaging: Superior photoacoustic and ultrasound endoscopy in live pigs using a transparent ultrasound transducer.

Dual-mode photoacoustic/ultrasound endoscopy (ePAUS) is a promising tool for preclinical and clinical interventions. To be clinically useful, ePAUS must deliver high-performance ultrasound imaging comparable to commercial systems and maintain high photoacoustic imaging performance at long working distances. This requires a transducer with an intact physical aperture and coaxial alignment of acoustic and optical beams within the probe, a challenging integration task. We present a high-performance ePAUS probe with a miniaturized, optically transparent ultrasonic transducer (TUT) called ePAUS-TUT. The 1.8-mm-diameter probe, fitting into standard endoscopic channels, aligns acoustic and optical beams efficiently, achieving commercial-level ultrasound and high-resolution photoacoustic imaging over long distances. These imaging capabilities were validated through in vivo imaging of a rat's rectum and a pig's esophagus. The ePAUS-TUT system substantially enhances feasibility and potential for clinical applications.

Finely tunable NIR‐II organic scaffolds for fluorescence/photoacoustic duplex imaging–guided noninvasive photothermal therapy of glioblastoma

AbstractOrganic agents possessing NIR‐II and photoacoustic duplex imaging capabilities, coupled with high‐efficiency photothermal conversion, offer significant potential for noninvasive and precise phototheranostics of glioblastoma, which is further augmented when these agents can concurrently exhibit tumor targeting and blood–brain barrier (BBB) permeability. This study reports a series of finely tunable NIR‐II molecular luminophores based on the aza‐BODIPY scaffold, featuring unique twisted and rotatable structures. They are further constructed to folate‐decorated polymeric nanoparticles, exhibiting remarkable NIR‐II/photoacoustic imaging performance and superior photothermal conversion efficiency (49.7%). Folate modification enables tumor targeting and BBB permeability through receptor‐mediated transcytosis, allowing for precise and efficient phototherapy in 4T1‐/glioblastoma‐bearing mice after a single intravenous injection and irradiation. This study presents a rational molecular engineering approach and a versatile structural scaffold for designing NIR‐II emitters with tailored photophysical properties and desirable phototherapeutic efficacy, thereby offering novel perspectives on the development of advanced depth imaging probes and brain tumor therapeutics.

Cationic conjugated polymer coupled non-conjugated segments for dually enhanced NIR-II fluorescence and lower-temperature photothermal-gas therapy

The lack of a simple design strategy to obtain ideal conjugated polymers (CPs) with high absorbance and fluorescence (FL) in the near-infrared-II (NIR-II; 1000–1700 nm) region still hampers the success of NIR-II light-triggered phototheranostics. Herein, novel phototheranostic nanoparticles (PPN-NO NPs) were successfully prepared by coloading a cationic NIR-II CPs (PBC-co-PBF-NMe3) and a NO donor (S-nitroso-N-acetylpenicillamine, SNAP) onto a 1:1 mixture of DSPE-PEG5000 and dimyristoylphosphatidylcholine (DMPC) for NIR-II FL and NIR-II photoacoustic (PA) imaging-guided low-temperature NIR-II photothermal therapy (PTT) and gas combination therapy for cancer treatment. A precise NIR-II FL dually enhanced design tactic was proposed herein by integrating flexible nonconjugated segments (C6) into the CPs backbone and incorporating quaternary ammonium salt cationic units into the CPs side chain, which considerably increased the radiative decay pathway, resulting in desirable NIR-II FL intensity and balanced NIR-II absorption and NIR PTT properties. The phototheranostic PPN-NO NPs exhibited distinguished NIR-II FL and PA imaging performance in tumor-bearing mice models. Furthermore, the low-temperature photothermal effect of PPN-NO NPs could initiate NO release upon 980 nm laser irradiation, efficiently suppressing tumor growth owing to the combination of low-temperature NIR-II PTT and NO gas therapy in vitro and in vivo.Graphical

Luciferase-Decorated Gold Nanorods as Dual-Modal Contrast Agents for Tumor-Targeted High-Performance Bioluminescence/Photoacoustic Imaging.

Gold nanorods (AuNRs) have been considered highly compelling materials for early cancer diagnosis and have aroused a burgeoning fascination among the biomedical sectors. By leveraging the versatile tunable optical properties of AuNRs, herein, we have developed a novel tumor-targeted dual-modal nanoprobe (FFA) that exhibits excellent bioluminescence and photoacoustic imaging performance for early tumor diagnosis. FFA has been synthesized by anchoring the recombinant bioluminescent firefly luciferase protein (Fluc) on the folate-conjugated AuNRs via the PEG linker. TEM images and UV-vis studies confirm the nanorod morphology and successful conjugation of the biomolecules to AuNRs. The nanoprobe FFA relies on the ability of the folate module to target the folate receptor-positive tumor cells actively, and simultaneously, the Fluc module facilitates excellent bioluminescent properties in physiological conditions. The success of chemical engineering in the present study enables stronger bioluminescent signals in the folate receptor-positive cells (Skov3, Hela, and MCF-7) than in folate receptor-negative cells (A549, 293T, MCF-10A, and HepG2). Additionally, the AuNRs induced strong photoacoustic conversion performance, enhancing the resolution of tumor imaging. No apparent toxicity was detected at the cellular and mouse tissue levels, manifesting the biocompatibility nature of the nanoprobe. Prompted by the positive merits of FFA, the in vivo animal studies were performed, and a notable enhancement was observed in the bioluminescent/photoacoustic intensity of the nanoprobe in the tumor region compared to that in the folate-blocking region. Therefore, this synergistic dual-modal bioluminescent and photoacoustic imaging platform holds great potential as a tumor-targeted contrast agent for early tumor diagnosis with high-performance imaging information.

A Method to Obtain the Transducers Impulse Response (TIR) in Photoacoustic Imaging

Photoacoustic tomography (PAT) is an emerging imaging technique with great potential for a wide range of biomedical imaging applications. The transducers impulse response (TIR) is a key factor affecting the performance of photoacoustic imaging (PAI). It is customary in PAI to assume that TIR is known or obtain it from experiments. In this paper, we investigate the possibility of obtaining TIR in another way. A new method is proposed to extract TIR from observed optoacoustic signal (OPAS) data, without prior knowledge, as a known condition. It is based on the relation between the OPAS data and the photoacoustic pressure signal (PAPS) at transducer positions. The relation can be expressed as a homogeneous linear equation. The TIR is solved by solving the homogeneous equation. The numerical test verifies the effectiveness of the presented method. This article also discusses the effect of calculation parameters on the extracting precision of TIR.

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

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. 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. 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. 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. 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.

Phantoms for evaluating the impact of skin pigmentation on photoacoustic imaging and oximetry performance.

Recent reports have raised concerns of potential racial disparities in performance of optical oximetry technologies. To investigate how variable epidermal melanin content affects performance of photoacoustic imaging (PAI) devices, we developed plastisol phantoms combining swappable skin-mimicking layers with a breast phantom containing either India ink or blood adjusted to 50-100% SO2 using sodium dithionite. Increasing skin pigmentation decreased maximum imaging depth by up to 25%, enhanced image clutter, and increased root-mean-square error in SO2 from 8.0 to 17.6% due to signal attenuation and spectral coloring effects. This phantom tool can aid in evaluating PAI device robustness to ensure high performance in all patients.

Machine learning assisted designing of Indacenodithiophene (IDT)-based polymers for future application of photoacoustic imaging

Non-invasive imaging tools are essential for diagnosis of complex disease. Photoacoustic (PA) imaging is a multiscale noninvasive imaging modality with high resolution and sensitivity for deep-seated pathologies. However, microenvironment of some pathologies produce PA signals compromising the optical resolution of PA imaging. This demands the construction of PA imaging agents to avoid the low signal to noise ratio with improved resolution and sensitivity. In this study, we use machine learning to design the IDT-based polymers with their absorption coefficient in NIR-I region. We used the database of polymer structures and properties to identify promising candidates for PAI. The models were then used to predict the properties of new IDT-based polymers with optimized absorption, biocompatibility and acoustic performance. Several promising candidates were identified and their in silico synthesis potential and PA imaging performance was predicted. The results demonstrates the potential of machine learning-guided polymers design for PA imaging agents and suggest that IDT-based polymers could be a valuable addition to the toolkit of PA imaging contrast agents.

A Cost-Effective Semiconducting Polymer with an Ether Chain-Substituted Bithiophene as the Donor Unit Enabling Effective NIR-II Photoacoustic Imaging

Due to their tunability in the chemical structure and light absorption, semiconducting polymers (SPs) have proven their promising potential for photoacoustic (PA) imaging within the second near-infrared (NIR-II) window. However, the syntheses of these polymers are generally lengthy and costly, limiting their potential applications. Herein, inspired by the commonly cost-effective thiophene-based compounds, we report a semiconducting polymer PTT-ATQ based on the non-fused ether chain-substituted donor unit 3,3′-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2′-bithiophene (TT). With the side chain substituted by the biocompatible ether chains, the TT unit possesses an even stronger electron-donating ability and thus, a strong intramolecular charge-transfer (ICT) effect in the polymer backbone; hence, an absorption band (peaked at ca. 1370 nm) within the NIR-II window for PTT-ATQ is realized. Meanwhile, the long and bulky side chains of the donor and acceptor units lead to a non-coplanarity in the polymer backbone, resulting in a twisted ICT effect that can induce high PA signals. Further results show that the PTT-ATQ has good biocompatibility and high in vivo PA imaging performance within the NIR-II window. This work highlights the effective strategy to realize high-performance NIR-II in vivo PA imaging SP contrast agents by using the cost-effective thiophene-based building blocks.

Optical and Photoacoustic Imaging In Vivo: Opportunities and Challenges.

Optical and photoacoustic imaging plays an important role in biomedical applications owing to its noninvasiveness and high resolution. Fluorescence imaging and photoacoustic imaging emerge as powerful tools to deconstruct molecular information and investigate biological processes in vivo. Despite great progress has been achieved in chemical probe synthesis, how to design probes with optimal fluorescence or photoacoustic imaging performance to dynamically visualize the biological process in vivo still faces challenges. From this perspective, we will focus on the advanced development of fluorescence and photoacoustic imaging in vivo. Furthermore, concerns and prospects for future imaging in vivo will be demonstrated.

131I labeled pH-responsive gold nanoparticles for bimodal tumor diagnosis

• Preparation of pH-responsive 131 I-labeled gold nano-particle molecular probe. • Aggregation of gold nanoparticles was explored based on the tumor microenvironment. • Dual-modality imaging further improves the diagnostic efficacy of tumors. Considering that each diagnostic method exhibits its disadvantages, such as the poor spatial resolution of SPECT and limited penetration depth of PA imaging, the development of a diagnosis integrated agent with dual-modality imaging performance is of great research interest. Herein, an interesting triggered mechanism, release, and aggregation of radiolabeled Au NPs were explored for tumor diagnosis based on the effect of H + in the tumor microenvironment. In vitro experiments reveal that the pH-responsive Au NPs exhibit an obvious accumulation effect and local surface plasmon resonance (LSPR) coupling effect and generate strong NIR absorption and can be used as the PA imaging agent. Importantly, Au aggregation only appears in the acid tumor microenvironment and displays excellent tumor SPECT diagnostic and photoacoustic imaging performance in vivo. This work provides a new synergistic strategy for SPECT and PA bimodal imaging to further improve the diagnostic efficacy of tumors.

An auto-photoacoustic melanin-based drug delivery nano-platform for self-monitoring of acute kidney injury therapy via a triple-collaborative strategy

Rhabdomyolysis-induced acute kidney injury (AKI) is closely related to toxic reactive oxygen species (ROS), apoptosis, and inflammation. Excessive activation of poly (ADP-ribose) polymerase-l (PARP-1) by ROS can cause mitochondrial dysfunction and release of the proapoptotic protein AIF, which triggers an intrinsic PARP-1-dependent cell death program. Considering these characteristics of rhabdomyolysis-induced AKI, we developed a targeting nanodrug delivery platform by loading PJ34 and coupling anti-GPR97 with melanin nanoparticles (GMP nanoparticles) that could realize photoacoustic self-monitoring and triple-collaborative treatment (antioxidant, antiapoptotic, and anti-inflammatory). The nanoparticles exhibited good dispersibility, solubility, and broad-spectrum ROS scavenging ability. In vitro experiments revealed high biocompatibility of the GMP nanoparticles and strong ability of scavenging multiple toxic ROS, antiapoptotic activity, and anti-inflammatory activity. Because melanin nanoparticles possess inherent photoacoustic (PA) imaging capability, they can not only serve as a drug carrier but also perform self-monitoring for real-time tracking of GMP biodistribution and renal uptake in a murine AKI model through PA imaging. In vivo experiments showed that the GMP nanoparticles could effectively reduce oxidative stress, apoptosis, and inflammatory response in mice with rhabdomyolysis-induced AKI, and the mechanism of alleviation was verified through western blot experiments. These results indicated that the nanoplatform could realize the targeted delivery and curative effect monitoring under the guidance of PA imaging, which is of great significance for the prevention and treatment of AKI. Statement of significanceA targeting nanodrug delivery platform was developed by loading PJ34 and coupling anti-GPR97 with melanin nanoparticles (GMP nanoparticles) for photoacoustic self-monitoring and triple-collaborative treatment (antioxidant, antiapoptotic, and anti-inflammatory) of acute kidney injury (AKI). Further studies indicated that the Keap-1/Nrf2/HO-1 and PARP-1/AIF signaling pathways are involved in the therapeutic mechanisms to alleviate AKI. Immunohistochemical staining and routine blood test confirmed the anti-inflammatory performance of GMP nanoparticles. Compared to exogenous nanomaterials, we used endogenous melanin with broad ROS scavenging capacity as the nanocarrier and antioxidant, which not only overcomes the defects of high specificity, potential toxicity, low loading capacity, and high cost but also shows good biosafety and photoacoustic imaging performance in vivo.

High Performance Gold Nanorods@DNA Self-Assembled Drug-Loading System for Cancer Thermo-Chemotherapy in the Second Near-Infrared Optical Window.

In terms of synergistic cancer therapy, biological nanomaterials with a second near-infrared (NIR-II) window response can greatly increase photothermal effects and photoacoustic imaging performance. Herein, we report a novel stimuli-responsive multifunctional drug-loading system which was constructed by integrating miniature gold nanorods (GNR) as the NIR-II photothermal nanorods and cyclic ternary aptamer (CTA) composition as a carrier for chemotherapy drugs. In this system, doxorubicin hydrochloride (DOX, a chemotherapy drug) binds to the G-C base pairs of the CTA, which exhibited a controlled release behavior based on the instability of G-C base pairs in the slightly acidic tumor microenvironment. Upon the 1064 nm (NIR-II biowindow) laser irradiation, the strong photothermal and promoted cargo release properties endow gold nanorods@CTA (GNR@CTA) nanoparticles displaying excellent synergistic anti-cancer effect. Moreover, the GNR@CTA of NIR also possesses thermal imaging and photoacoustic (PA) imaging properties due to the strong NIR region absorbance. This work enables to obtaining a stimuli-responsive “all-in-one” nanocarrier, which are promising candidate for bimodal imaging diagnosis and chemo-photothermal synergistic therapy.

Food-Grade Activated Charcoal for Contrast-Enhanced Photoacoustic Imaging of Aspiration: A Phantom Study.

Aspiration pneumonia has the highest attributable mortality of all medical complications post-stroke, or in individuals with progressive neurological diseases. For optimum health outcomes for individuals with dysphagia, a non-invasive and convenient method for objectively detecting aspiration is needed. This study introduces a potential new aspiration screening method based on photoacoustic imaging (PAI), a medical imaging technology that measures the optical contrast of tissue rather than mechanical or elastic properties. In this preliminary study, a tissue-mimicking neck phantom was designed to test the performance of PAI for aspiration screening with a charcoal solution as a contrast agent. A 1064nm wavelength light source was illuminated on the anterior of the neck phantom to induce the photoacoustic effect. The resulting photoacoustic signal of the charcoal contrast in the mock trachea was detected by a linear transducer array with a 2.25MHz central ultrasound frequency. The phantom results showed that charcoal solution at 10mg/ml exhibited strong photoacoustic signals when flowing into the phantom trachea. By overlaying the photoacoustic signals of the charcoal contrast on top of the ultrasound image, we were able to simultaneously visualize the movement of food contrast and a cross-section of tissue structures during mock swallowing. Moreover, we confirmed the ability to detect the flow of charcoal contrast at a small bolus volume of ~ 7 μl through the phantom, suggesting high sensitivity to detect small aspiration events. The study suggests that PAI holds promise to be developed as an aspiration detection tool with charcoal powder as a contrast agent.

Photoacoustic response optimization of gold nanorods in the near-infrared region

Photoacoustic imaging (PAI) combines the advantage of optical and ultrasonic imaging, which has a high signal-to-noise ratio, and spatial resolution. To further improve the performance of PAI, gold nanorods can be utilized as exogenous contrast agents, and their size can be controlled. The size change of gold nanorods will change their absorption and heat transfer characteristics, and then affect their photoacoustic characteristics. Therefore, in the present work, the influences of absorption characteristics (absorption cross section and volume absorption coefficient) and heat transfer characteristics (specific surface area) of gold nanorods on photoacoustic response are studied by FDTD (FDTD Solutions, Lumerical) and FEM (Comsol Multiphysics). Results show that the increase of specific surface area will enhance the thermal coupling between gold nanorods and water, so as to improve the heat transfer and produce different photothermal responses without significantly affecting the photoacoustic quantum yield (As the specific surface area increases by about 10 times, the temperature increases by about 12 times, while the photoacoustic quantum yield increases by about 24%). On the contrary, absorption characteristics are decisive factors for both photothermal and photoacoustic responses. Therefore, in terms of improving photoacoustic quantum yield, when the size of gold nanorods changes, more attention should be paid to the improvement of the absorption characteristics rather than the specific surface area. In addition, increasing the specific surface area can significantly improve the photostability of gold nanorods, which is very important for practical applications.

NIR-II Functional Materials for Photoacoustic Theranostics.

Photoacoustic imaging (PAI) has attracted great attention in the diagnosis and treatment of diseases due to its noninvasive properties. Especially in the second near-infrared (NIR-II) window, PAI can effectively avoid the interference of tissue spontaneous fluorescence and light scattering, and obtain high resolution images with deeper penetration depth. Because of its ideal spectral absorption and high conversion efficiency, NIR-II PA contrast agents overcome the absorption or emission of NIR-II light by endogenous biomolecules. In recent years, a series of NIR-II PA contrast agents have been developed to improve the performance of PAI in disease diagnosis and treatment. In this paper, the research progress of NIR-II PA contrast agents and their applications in biomedicine are reviewed. PA contrast agents are classified according to their composition, including inorganic contrast agents, organic contrast agents, and hybrid organic-inorganic contrast agents. The applications of NIR-II PA contrast agents in medical imaging are described, such as cancer imaging, inflammation detection, brain disease imaging, blood related disease imaging, and other biomedical application. Finally, the research prospects and breakthrough of NIR-II PA contrast agents are discussed.

Targeted contrast agents and activatable probes for photoacoustic imaging of cancer.

Photoacoustic (PA) imaging has emerged as a powerful technique for the high resolution visualization of biological processes within deep tissue. Through the development and application of exogenous targeted contrast agents and activatable probes that can respond to a given cancer biomarker, researchers can image molecular events in vivo during cancer progression. This information can provide valuable details that can facilitate cancer diagnosis and therapy monitoring. In this tutorial review, we provide a step-by-step guide to select a cancer biomarker and subsequent approaches to design imaging agents for in vivo use. We envision this information will be a useful summary to those in the field, new members to the community, and graduate students taking advanced imaging coursework. We also highlight notable examples from the recent literature, with emphasis on the molecular designs and their in vivo PA imaging performance. To conclude, we provide our outlook and future perspective in this exciting field.

Selenium Vacancy Engineering Using Bi2Se3 Nanodots for Boosting Highly Efficient Photonic Hyperthermia.

Despite bismuth-based energy conversion nanomaterials having attracted extensive attention for nanomedicine, the nanomaterials suffer from major shortcomings including low tumor accumulation, long internal retention time, and undesirable photothermal conversion efficiency (PCE). To combat these challenges, bovine serum albumin and folic acid co-modified Bi2Se3 nanomedicine with rich selenium vacancies (abbreviated as VSe-BS) was fabricated for the second near-infrared (NIR-II) light-triggered photonic hyperthermia. More importantly, selenium vacancies on the crystal planes (0 1 5) and (0 1 11) of VSe-BS with similar formation energies could be distinctively observed via aberration-corrected scanning transmission electron microscopy images. The defect engineering endows VSe-BS with enhanced conductivity, making VSe-BS possess outstanding PCE (54.1%) in the NIR-II biowindow and desirable photoacoustic imaging performance. Tumor ablation studies indicate that VSe-BS possesses satisfactory therapeutic outcomes triggered by NIR-II light. These findings give rise to inspiration for further broadening the biological applications of defect engineering bismuth-based nanomaterials.

A Novel Biomimetic Nanoprobe as a Photoacoustic Contrast Agent.

Specific detection of tumors is of pivotal importance to cancer prevention and therapy yet a big challenge. Photoacoustic imaging (PAI) as an emerging non-invasive modality has shown great potential in biomedical and clinical applications. The performance of PAI largely depends on the light-absorption coefficient of the imaged tissue and the PAI contrast agent being used, either endogenously or exogenously. The exogenous contrast agents developed so far have greatly helped to improve PAI, but still have some limitations, such as lack of targeting capacity and easy clearance by the host immune system. Herein, we fabricated a biomimetic nanoprobe with cell membrane coating as a novel PAI contrast agent, namely, MPD [membrane-coated poly(lactic-co-glycolic acid) (PLGA)/dye]. In brief, the organic dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR) was encapsulated by the Food and Drug Administration–approved polymer, poly(lactic-co-glycolic acid) (PLGA), to form polymer nanoparticles by emulsification. The nanoparticles are further coated with the cancer cell membrane to form MPD. MPD has outstanding biocompatibility, tumor specificity, and in vivo stability. Thus, MPD is a versatile NIR-I theranostic nanoplatform for PAI-guided cancer diagnosis and therapy.

Organic Semiconducting Macromolecular Dyes for NIR‐II Photoacoustic Imaging and Photothermal Therapy

AbstractOwing to the unique advantages of photoacoustic imaging (PAI) and photothermal therapy (PTT) conducted over the near‐infrared‐II (NIR‐II) window, the development of high‐efficiency optical agents with NIR‐II light responsiveness is of great significance. Despite the diversity of optical agents developed for NIR‐II PAI and PTT, most of them are based on inorganic nanomaterials and small molecular dyes, whose biosafety and photostability need to be further assessed, respectively. Organic semiconducting macromolecular dyes (OSMDs) featuring a large semiconducting backbone are becoming alternative candidates for NIR‐II PAI and PTT owing to their reliable biocompatibility, durable photostability, and ideal photothermal conversion capability. This paper reviews the current progress of OSMD‐based PAI and PTT in the NIR‐II optical window. The three main types of OSMDs with different skeleton architectures are introduced, and their applications for NIR‐II PAI (tumor imaging, stem cell tracking, and vasculature imaging) and PTT (tumor ablation) are described. Viable strategies for further improving the NIR‐II PAI performance of OSMDs are discussed. Finally, some major issues faced by OSMDs in NIR‐II PAI and PTT are raised, and the future development directions of OSMDs are analyzed.