Cancer Cell Membrane Camouflaged Nanoprobe for Catalytic Ratiometric Photoacoustic Imaging of MicroRNA in Living Mice

Herein, a cancer cell (MCF‐7 cell) membrane‐encapsulated dendritic mesoporous silica nanoparticle simultaneously functionalized with DNA‐photoacoustic (DNA‐PA) probes and glutathione (GSH)‐responsive DNA fuel strands for PA imaging of tumor‐related miRNA in living mice with signal amplification ability is developed. It is demonstrated that one target miRNA can trigger disassembly of multiple PA fluorophore probes from the quencher with the aid of GSH‐responsive DNA fuel strands via the entropy‐driven process, resulting remarkable amplified change of PA signal ratio. Using oncogenic miRNA‐21 as a model, a linear relationship between miRNA‐21 concentrations and PA ratio in a dynamic range from 10 × 10^?12 m to 100 × 10^?9 m and a limit of detection down to 11.69 × 10^?12 m are established. The accurate PA signal observation related to miRNA‐21s in the tumor area in living mice is demonstrated, and the PA signal ratio increases significantly via the injection of miRNA‐21. It is anticipated that the catalytic ratiometric PA imaging system can be applied to an array of molecular detection in living system by rational detection probe design.     

Photoacoustic Probes for Molecular Detection: Recent Advances and Perspectives

Photoacoustic (PA) imaging (PAI) is a noninvasive and nonionizing biomedical imaging modality that combines the advantages of optical imaging and ultrasound imaging. Based on PAI, photoacoustic detection (PAD) is an emerging approach that is involved with the interaction between PA probes and analytes resulting in the changes of photoacoustic signals for molecular detection with rich contrast, high resolution, and deep tissue penetration. This Review focuses on the recent development of PA probes in PAD. The following contents will be discussed in detail: 1) the construction of PA probes; 2) the applications and mechanisms of PAD to different types of analytes, including microenvironments, small biomolecules, or metal ions; 3) the challenges and perspectives of PA probes in PAD.     

Activatable Semiconducting Theranostics: Simultaneous Generation and Ratiometric Photoacoustic Imaging of Reactive Oxygen Species In Vivo

Enhancing the generation of reactive oxygen species (ROS) is an effective anticancer strategy. However, it is a great challenge to control the production and to image ROS in vivo, both of which are vital for improving the efficacy and accuracy of cancer therapy. Herein, an activatable semiconducting theranostic nanoparticle (NP) platform is developed that can simultaneously enhance ROS generation while self‐monitoring its levels through ratiometric photoacoustic (PA) imaging. The NP platform can further guide in vivo therapeutic effect in tumors. The theranostic NP platform is composed of: (i) cisplatin prodrug and ferric ion catalyst for ROS generation, a part of combination cancer therapy; and (ii) a ratiometric PA imaging nanoprobe consisting of inert semiconducting perylene‐diimide (PDI) and ROS activatable near‐infrared dye (IR790s), used in ratiometric PA imaging of ROS during cancer treatment. Ratiometric PA signals are measured at two near‐infrared excitation wavelengths: 680 and 790 nm for PDI and IR790s, respectively. The measurements show highly accurate visualization of ^?OH generation in vivo. This novel ROS responsive organic theranostic NP allows not only synergistic cancer chemotherapy but also real‐time monitoring of the therapeutic effect through ratiometric PA imaging.     

A Single Composition Architecture‐Based Nanoprobe for Ratiometric Photoacoustic Imaging of Glutathione (GSH) in Living Mice

As one of the reduction species, glutathione (GSH) plays a tremendous role in regulating the homeostasis of redox state in living body. Accurate imaging of GSH in vivo is highly desired to provide a real‐time visualization of physiological and pathological conditions while it is still a big challenge. Recently developed photoacoustic imaging (PAI) with high resolution and deep penetration characteristics is more promising for in vivo GSH detection. However, its application is dramatically limited by the difficult designation of photoacoustic probes with changeable near‐infrared (NIR)‐absorption under reductive activation. A cyanine derivative‐based activatable probe is developed for in vivo ratiometric PAI of GSH for the first time. The probe is structurally designed to output ratiometric signals toward GSH in NIR‐absorption region based on the cleavage of disulfide bond followed by a subsequent exchange between the secondary amine and sulfydryl group formed. Such a ratiometric manner provides high signal‐to‐noise imaging of blood vessels and their surrounding areas in tumor. Concomitantly, it also exhibits good specificity toward GSH over other thiols. Furthermore, the single composition architecture of the probe effectively overcomes the leakage issue compared with traditional multicomposition architecture‐based nanoprobe, thus enhancing the imaging accuracy and fidelity in living body.     

In Vivo Chemoselective Photoacoustic Imaging of Copper(II) in Plant and Animal Subjects

The detection of Cu²⁺ in living plants and animals is of great importance for environment monitoring and disease diagnosis. Here, a near‐infrared (NIR) turn‐on photoacoustic (PA) probe (denoted as LET‐2) is developed for Cu²⁺ detection in living subjects, such as soybean sprouts and mice. The absorbance band of LET‐2 shifts from 625 to 715 nm after the interaction with Cu²⁺, thus producing strong PA signal output at 715 nm (PA₇₁₅) as an indicator. The PA₇₁₅ value is increased as a function of the concentration of Cu²⁺ (0 × 10^?6–20 × 10^?6m ), with a calculated limit of detection of 10.8 × 10^?9m . More importantly, both in vitro and in vivo studies in soybean sprouts and mice indicate that the as‐prepared LET‐2 PA probe is highly sensitive and selective for Cu²⁺ detection. These findings provide a solution for in vivo detection of metal ions by using chemoselective PA probes.     

Molecular Engineering of Photoacoustic Performance by Chalcogenide Variation in Conjugated Polymer Nanoparticles for Brain Vascular Imaging

As conjugated polymer nanoparticles (CPNs) have attracted growing interest as photoacoustic (PA) imaging contrast agents, revelation of the relationship between the molecular structure of conjugated polymers and PA property is highly in demand. Here, three donor–acceptor‐structured conjugated polymer analogs are designed, where only a single heteroatom of acceptor units changes from oxygen to sulfur to selenium, allowing for systematic investigation of the molecular structure–PA property relationship. The absorption and PA spectra of these CPNs can be facilely tuned by changing the heteroatoms of the acceptor units. Moreover, the absorption coefficient, and in turn the PA signal intensity, decreases when the heteroatom changes from oxygen to sulfur to selenium. As these CPNs exhibit weak fluorescence and similar photothermal conversion efficiency (≈70%), their PA intensities are approximately proportional to their absorption coefficients. The in vivo brain vasculature imaging in this study also demonstrates this trend. This study provides a simple but efficient strategy to manipulate the PA properties of CPNs through changing the heteroatom at key positions.     

基于光声技术的火灾气体探测系统设计

近年来，针对标识性气体的探测成为火灾探测技术中发展最活跃的领域之一。将可检测极低浓度的某一气体的光声检测技术应用于极早期火灾气体产物的检测是一个新的尝试，将可能实现高灵敏度、高可靠性的火灾探测。但常规光声气体检测设备结构复杂、价格昂贵，必须恰当的重新设计才能应用到火灾探测系统中。分析了该技术在火灾探测中应用的关键问题,并提出了一种利用光声腔和光源间的“自由吸收路径”进行测量的光声气体探测系统，避免了对光源的窄带滤波要求，实现了在线式的气体检测。起始状态下，光声腔密封有纯CO气体，吸收光源中4.6 μm的辐射，产生一定强度的初始光声信号；当火灾气体产物流经吸收路径时，其中的CO气体吸收使到达光声腔的光辐射在4.6 μm波长上发生衰减，导致光声信号减弱，这个信号的变化量就反映了吸收路径中的CO气体浓度。     

Biosynthesis of Melanin Nanoparticles for Photoacoustic Imaging Guided Photothermal Therapy

Photothermal therapy (PTT) has attracted considerable attention in recent years due to their unique advantages in minimal invasiveness and spatiotemporal selectivity. However, the fabrication procedures of PTT agents frequently require complex chemical and/or physical methods that involves harsh and environmentally hazardous conditions. Here, a genetically engineered bacterium is developed to synthesize melanin nanoparticles under mild and environmentally friendly conditions. The biosynthetic melanin nanoparticles exhibit excellent biocompatibility, good stability, and negligible toxicity. In addition, the biosynthetic melanin nanoparticles have strong absorption at near-infrared (NIR) region and higher photothermal conversion efficiency (48.9%) than chemically synthesized melanin-like polydopamine nanoparticles under an 808 nm laser irradiation. Moreover, the results show that the biosynthetic melanin nanoparticles have excellent photoacoustic imaging (PAI) performance and can be used for PAI guided PTT in vivo. In conclusion, the study provides an alternative approach to synthesize PTT agents with broad application potential in the diagnosis and treatment of cancer.     

Second Near-Infrared Plasmonic Nanomaterials for Photoacoustic Imaging and Photothermal Therapy

Photoacoustic imaging (PAI) and imaging-guided photothermal therapy (PTT) in the second near-infrared window (NIR-II, 1000–1700 nm) have received increasing attention owing to their advantages of greater penetration depth and higher signal-to-noise ratio. Plasmonic nanomaterials with tunable optical properties and strong light absorption provide an alternative to dye molecules, showing great prospects for phototheranostic applications. In this review, the research progress in principally modulating the optical properties of plasmonic nanomaterials, especially affecting parameters such as size, morphology, and surface chemical modification, is introduced. The commonly used plasmonic nanomaterials in the NIR-II window, including noble metals, semiconductors, and heterostructures, are then summarized. In addition, the biomedical applications of these NIR-II plasmonic nanomaterials for PAI and PTT in phototheranostics are highlighted. Finally, the perspectives and challenges for advancing plasmonic nanomaterials for practical use and clinical translation are discussed.     

Advanced Photoacoustic Imaging Applications of Near‐Infrared Absorbing Organic Nanoparticles

Progress of nanotechnology in recent years has stimulated fast development of nanoparticles in biomedical research. Photoacoustic (PA) imaging as an emerging non‐invasive technique in molecular imaging has improved imaging depth relative to conventional optical imaging, demonstrating great potential in clinical applications. The convergence of nanotechnology and PA imaging has enabled a broad spectrum of new opportunities in fundamental biology and translation medicine. This review focuses on the recent advances of organic nanoparticles in PA imaging applications. Near‐infrared absorbing organic nanoparticles are classified and discussed according to their different imaging applications, which include tumor imaging, gastrointestinal imaging, sentinel lymph node imaging, disease microenvironment imaging and real‐time drug imaging. The chemistry and PA properties of organic nanoparticles are discussed in details to highlight their own merits, and their challenges and perspectives in PA imaging are also discussed.     

Fluorescence Quenching Nanoprobes Dedicated to In Vivo Photoacoustic Imaging and High‐Efficient Tumor Therapy in Deep‐Seated Tissue

Photoacoustic imaging (PAI) and photoacoustic (PA) therapy have promising applications for treating tumors. It is known that the utilization of high‐absorption‐coefficient probes can selectively enhance the PAI target contrast and PA tumor therapy efficiency in deep‐seated tissue. Here, the design of a probe with the highest availability of optical‐thermo conversion by using graphene oxide (GO) and dyes via π–π stacking interactions is reported. The GO serves as a base material for loading dyes and quenching dye fluorescence via fluorescence resonance energy transfer (FRET), with the one purpose of maximum of PA efficiency. Experiments verify that the designed fluorescence quenching nanoprobes can produce stronger PA signals than the sum of the separate signals generated in the dye and the GO. Potential applications of the fluorescence quenching nanoprobes are demonstrated, dedicating to enhance PA contrast of targets in deep‐seated tissues and tumors in living mice. PA therapy efficiency both in vitro and in vivo by using the fluorescence quenching nanoprobes is found to be higher than with the commonly used PA therapy agents. Taken together, quenching dye fluorescence via FRET will provide a valid means for developing high‐efficiency PA probes. Fluorescence quenching nanoprobes are likely to become a promising candidate for deep‐seated tumor imaging and therapy.