抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The near-infrared window between 1000 and 1700 nm, commonly termed the "second near-infrared (NIR-II) window," has quickly emerged as a highly attractive optical region for biological imaging. In contrast to conventional imaging in the visible region between 400 and 700 nm, as well as in the first NIR (NIR-I) window between 700 and 900 nm, NIR-II biological imaging offers numerous merits, including higher spatial resolution, deeper penetration depth, and lower optical absorption and scattering from biological substrates with minimal tissue autofluorescence. Noninvasive imaging techniques, specifically NIR-II fluorescence and photoacoustic (PA) imaging, have embodied the attractiveness of NIR-II optical imaging, with several NIR-II contrast agents demonstrating superior performance to the clinically approved NIR-I agents. Consequently, NIR-II biological imaging has been increasingly explored due to its tremendous potential for preclinical studies and clinical utility. Herein, the progress of optical imaging in the NIR-II window is reported. Starting with highlighting the importance of biological imaging in the NIR-II spectral region, the emergence and latest development of various NIR-II fluorescence and PA imaging probes and their applications are then discussed. Perspectives on the promises and challenges facing this nascent yet exciting field are then given.

Recent Advances of Optical Imaging in the Second Near-Infrared Window

Photoacoustic (PA) imaging as a fast-developing imaging technique has great potential in biomedical and clinical applications. It is a noninvasive imaging modality that depends on the light-absorption coefficient of the imaged tissue and the injected PA-imaging contrast agents. Furthermore, PA imaging provides superb contrast, super spatial resolution, and high penetrability and sensitivity to tissue functional characteristics by detecting the acoustic wave to construct PA images. In recent years, a series of PA-imaging contrast agents are developed to improve the PA-imaging performance in biomedical applications. Here, recent progress of PA contrast agents and their biomedical applications are outlined. PA contrast agents are classified according to their components and function, and gold nanocrystals, gold-nanocrystal assembly, transition-metal chalcogenides/MXene-based nanomaterials, carbon-based nanomaterials, other inorganic imaging agents, small organic molecules, semiconducting polymer nanoparticles, and nonlinear PA-imaging contrast agents are discussed. The applications of PA contrast agents as biosensors (in the sensing of metal ions, pH, enzymes, temperature, hypoxia, reactive oxygen species, and reactive nitrogen species) and in bioimaging (lymph nodes, vasculature, tumors, and brain tissue) are discussed in detail. Finally, an outlook on the future research and investigation of PA-imaging contrast agents and their significance in biomedical research is presented.

Photoacoustic Imaging: Contrast Agents and Their Biomedical Applications.

Fluorescence and photoacoustic imaging have different advantages in cancer diagnosis; however, combining effects in one agent normally requires a trade-off as the mechanisms interfere. Here, based on rational molecular design, we introduce a smart organic nanoparticle whose absorbed excitation energy can be photo-switched to the pathway of thermal deactivation for photoacoustic imaging, or to allow opposed routes for fluorescence imaging and photodynamic therapy. The molecule is made of a dithienylethene (DTE) core with two surrounding 2-(1-(4-(1,2,2-triphenylvinyl)phenyl)ethylidene)malononitrile (TPECM) units (DTE-TPECM). The photosensitive molecule changes from a ring-closed, for photoacoustic imaging, to a ring-opened state for fluorescence and photodynamic effects upon an external light trigger. The nanoparticles' photoacoustic and fluorescence imaging properties demonstrate the advantage of the switch. The use of the nanoparticles improves the outcomes of in vivo cancer surgery using preoperative photoacoustic imaging and intraoperative fluorescent visualization/photodynamic therapy of residual tumours to ensure total tumour removal.

/pdf/light-driven-transformable-optical-agent-with-adaptive-4e2dgn40mv.pdf

Light-driven transformable optical agent with adaptive functions for boosting cancer surgery outcomes

Phototherapies including photothermal therapy (PTT) and photodynamic therapy (PDT) have gained considerable attention due to their high tumor ablation efficiency, excellent spatial resolution and minimal side effects on normal tissue. In contrast to inorganic nanoparticles, near-infrared (NIR) absorbing organic nanoparticles bypass the issue of metal-ion induced toxicity and thus are generally considered to be more biocompatible. Moreover, with the guidance of different kinds of imaging methods, the efficacy of cancer phototherapy based on organic nanoparticles has shown to be optimizable. In this review, we summarize the synthesis and application of NIR-absorbing organic nanoparticles as phototherapeutic nanoagents for cancer phototherapy. The chemistry, optical properties and therapeutic efficacies of organic nanoparticles are firstly described. Their phototherapy applications are then surveyed in terms of therapeutic modalities, which include PTT, PDT and PTT/PDT combined therapy. Finally, the present challenges and potential of imaging guided PTT/PDT are discussed.

/pdf/recent-progress-in-the-development-of-near-infrared-organic-2x0l2utwjz.pdf

Recent progress in the development of near-infrared organic photothermal and photodynamic nanotherapeutics.

Photoacoustic Molecular Imaging: From Multiscale Biomedical Applications Towards Early-Stage Theranostics

The delineation of brain gliomas margins still poses challenges to precise imaging and targeted therapy, mainly due to strong light attenuation of the skull and high background interference. With deep penetration and high sensitivity, photoacoustic (PA) imaging (PAI) in the second near-infrared (NIR II) window holds great potential for brain gliomas imaging. Herein, mesoionic dye A1094 encapsulated in Arg-Gly-Asp-modified hepatitis B virus core protein (RGD-HBc) is designed and synthesized for effective NIR II PAI of brain gliomas. An aggregation-induced absorption enhancement mechanism is discovered in vitro and in vivo. It is also demonstrated that A1094@RGD-HBc, with an enhanced absorption in the NIR II window, displays ninefold PA signal amplification in vivo, allowing for precise PAI of the brain gliomas at a depth up to 5.9 mm. In addition, with the application of abovementioned agent, high-resolution PAI and ultrasensitive single photon emission computed tomography images of brain gliomas are acquired with accurate co-localization. Collectively, the results suggest great promise of A1094@RGD-HBc for diagnostic imaging and precise delineation of brain gliomas in clinical applications.

https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.201801615

Aggregation-Induced Absorption Enhancement for Deep Near-Infrared II Photoacoustic Imaging of Brain Gliomas In Vivo

With high optical absorption efficiency, near infrared (NIR) dyes have been proposed as theranostic agents for fluorescence imaging, photoacoustic imaging (PAI), and photothermal therapy (PTT). However, inherent hydrophobicity and short circulation time of small molecule hinder the further biomedical application. Herein smart amphiphilic copolymer was synthesized containing IR780/camptothecin@poly(e-caprolactone) (IR780/CPT@PCL) as core, helical poly(phenyl isocyanide) (PPI) blocks as shell with the pH-responsive rhodamine B (RhB) moieties in the core-shell interface. With hydrophilic helical PPI coronas, these micelles present significantly enhanced cell-penetrating capacity that plays a key role in facilitating intracellular delivery of various cargos. By encapsulating CPT and IR780 molecules, the multifunctional self-assemble probe has huge potential to realize functional cooperativity and adaptability for cancer diagnosis and therapy. The in vitro and in vivo experimental results demonstrate that the pH-triggered fluorescent responsiveness and strong acoustic generation permit them efficient fluorescent and PA signal sensing for cancer diagnosis. Moreover, with 808 nm laser irradiation, the generated heat significantly improves the drug release from PCL core, leading to synergetic chemo-photothermal therapy and decreases tumor recurrence rates in mice. Overall, the biocompatible multifunctional micelles with these combined advantages can potentially be utilized for PAI guided disease diagnosis and tumor ablation.

Versatile pH-response Micelles with High Cell-Penetrating Helical Diblock Copolymers for Photoacoustic Imaging Guided Synergistic Chemo-Photothermal Therapy

Highly-efficient targeting probes are desirable for disease diagnosis and functional imaging. However, most of the current near-infrared (NIR) probes suffer from low signal conversion, insufficient photostability, poor probe specificity, and limited functions. Herein, an NIR ultrahigh absorbing croconium dye for amyloid (CDA) was designed and synthesized to specifically bind to cerebrovascular amyloid without antibody linkage. This unique CDA is able to strongly bind the hydrophobic channels of amyloid beta (Aβ) fiber with a very strong binding energy of -9.3 kcal mol-1. Our experimental results demonstrate that the amphipathic dye with an intense absorption peak at 800 nm generated a significant local temperature surge under low-power laser irradiation. Compared with representative prominent indocyanine green, Prussian blue, and gold nanorods, this probe can produce the strongest photoacoustic signal based on the same mass concentration. Labeled with radioactive 18F, this multifunctional probe allowed for the ultrasensitive photoacoustic tomography (PAT)/positron emission tomography (PET)/fluorescence imaging of Aβ plaques in the brain cortex. Featured with high spatial resolution and optical specificity, PAT was intrinsically suitable for imaging pathological sites on cortical vessels, whereas PET revealed whole-body anatomy with quantitative biodistribution information. Our study shows that a CDA-based functionalized dye aided with PAT and PET is capable of plaque diagnosis and localization.

/pdf/highly-specific-noninvasive-photoacoustic-and-positron-4fglzs0qit.pdf

Highly specific noninvasive photoacoustic and positron emission tomography of brain plaque with functionalized croconium dye labeled by a radiotracer.

Diagnosing cancer during early stages can substantially increase the cure rate, decrease the recurrence rate, and reduce health care costs. Over the past few decades, the continual development of new medical imaging modalities has been an important factor for diagnosing cancer, selecting therapies, and monitoring response to treatment. Photoacoustic tomography (PAT) is a hybrid imaging modality combining optical contrast from absorption of light with the outstanding spatiotemporal resolution of US imaging, providing biomedical morphologic and functional information of early-stage cancer. In this review, the basics and modalities of PAT, as well as a summary of its state-of-art applications in early-stage cancer (breast cancer, melanoma, and prostate cancer) detection and treatment guidance will be introduced. The potential clinical translation in cancer detection of PAT and prospects for the possibilities to lead to further clinical breakthroughs will also be discussed. Keywords: Molecular Imaging-Cancer, Photoacoustic Imaging © RSNA, 2020.

https://pubs.rsna.org/doi/pdf/10.1148/rycan.2020190030

Yajing Liu

Papers

Photoacoustic Molecular Imaging: From Multiscale Biomedical Applications Towards Early-Stage Theranostics

Aggregation-Induced Absorption Enhancement for Deep Near-Infrared II Photoacoustic Imaging of Brain Gliomas In Vivo

Versatile pH-response Micelles with High Cell-Penetrating Helical Diblock Copolymers for Photoacoustic Imaging Guided Synergistic Chemo-Photothermal Therapy

Highly specific noninvasive photoacoustic and positron emission tomography of brain plaque with functionalized croconium dye labeled by a radiotracer.

High-Resolution Photoacoustic Tomography for Early-Stage Cancer Detection and Its Clinical Translation.