General Post-Regulation Strategy of AIEgens' Photophysical Properties for Intravital Two-Photon Fluorescence Imaging.

Fluorogens with aggregation-induced emission (AIEgens) are promising agents for two-photon fluorescence (TPF) imaging. However, AIEgens' photophysical properties are fixed and unoptimizable once synthesized. Therefore, it is urgent and meaningful to explore an efficient post-regulation strategy to optimize AIEgens' photophysical properties.

in vivo and in situ robust quantitative optical biopsy of hepatocellular carcinoma and metastasis based on two-photon autofluorescence imaging.

Two-photon autofluorescence (TPAF) imaging is able to offer precise cellular metabolic information with high spatiotemporal resolution, making it a promising biopsy tool. The technique is greatly hampered by the complexity of either the optical system or data processing. Here, the excitation wavelength was optimized to simultaneously excite both flavin adenine dinucleotide and nicotinamide adenine dinucleotide and eliminate the unexpected TPAF.

Boosted photo-immunotherapy near-infrared light excited phototherapy in tumor sites and photo-activation in sentinel lymph nodes.

Phototherapy is a promising modality that could eradicate tumor and trigger immune responses immunogenic cell death (ICD) to enhance anti-tumor immunity. However, due to the lack of deep-tissue-excitable phototherapeutic agents and appropriate excitation strategies, the utility of phototherapy for efficient activation of the immune system is challenging. Herein, we report functionalized ICG nanoparticles (NPs) with the capture capability of tumor-associated antigens (TAAs).

Data-driven coordinated attention deep learning for high-fidelity brain imaging denoising and inpainting.

Deep learning offers promise in enhancing low-quality images by addressing weak fluorescence signals, especially in deep in vivo mouse brain imaging. However, current methods struggle with photon scarcity and noise within in vivo deep mouse brains, and often neglecting tissue preservation. In this study, we propose an innovative in vivo cortical fluorescence image restoration approach, combining signal enhancement, denoising, and inpainting.

Biocompatible polymer optical fiber with a strongly scattering spherical end for interstitial photodynamic therapy.

Interstitial photodynamic therapy (I-PDT), which utilizes optical fibers to deliver light for photosensitizer excitation and the elimination of penetration depth limitation, is a promising modality in the treatment of deeply seated tumors or thick tumors. Currently, the excitation domain of the optical fiber is extremely limited, restricting PDT performance. Here, we designed and fabricated a biocompatible polymer optical fiber (POF) with a strongly scattering spherical end (SSSE) for I-PDT applications, achieving an increased excitation domain and consequently excellent in vitro and in vivo therapeutical outcomes.

Advanced flow cytometry for biomedical applications.

Flow cytometry (FC) is a versatile tool with excellent capabilities to detect and measure multiple characteristics of a population of cells or particles. Notable advancements in in vivo photoacoustic FC, coherent Raman FC, microfluidic FC, and so on, have been achieved in the last two decades, which endows FC with new functions and expands its applications in basic research and clinical practice. Advanced FC broadens the tools available to researchers to conduct research involving cancer detection, microbiology (COVID-19, HIV, bacteria, etc.

Superior biocompatible carbon dots for dynamic fluorescence imaging of nucleoli in living cells.

The nucleolus is a newly developed and promising target for cancer diagnosis and therapy, and its imaging is extremely significant for fundamental research and clinical applications. The unique feature, , high resolution at the subcellular level, makes the fluorescence imaging method a powerful tool for nucleolus imaging. However, the fluorescence imaging of nucleoli in living cells is restricted by the limited availability of fluorescent agents with specific nucleolus-targeting capability and superior biocompatibility.

The stiffness-dependent tumor cell internalization of liquid metal nanoparticles.

The properties of nanoparticle (NP) carriers, such as size, shape and surface state, have been proven to dramatically affect their uptake by tumor cells, thereby influencing and determining the effect of nanomedicine on tumor theranostics. However, the effect of the stiffness of NPs on their cellular internalization remains unclear, especially for circumstances involving active or passive NP targeting. In this work, we constructed eutectic gallium indium liquid metal NPs with the same particle size, shape and surface charge properties but distinct stiffness tailoring the surface oxidation and silica coating.

Light amplified oxidative stress in tumor microenvironment by carbonized hemin nanoparticles for boosting photodynamic anticancer therapy.

Photodynamic therapy (PDT), which utilizes light excite photosensitizers (PSs) to generate reactive oxygen species (ROS) and consequently ablate cancer cells or diseased tissue, has attracted a great deal of attention in the last decades due to its unique advantages. However, the advancement of PDT is restricted by the inherent characteristics of PS and tumor microenvironment (TME). It is urgent to explore high-performance PSs with TME regulation capability and subsequently improve the therapeutic outcomes.

Noninvasive and early diagnosis of acquired brain injury using fluorescence imaging in the NIR-II window.

Acquired brain injury (ABI), which is the umbrella term for all brain injuries, is one of the most dangerous diseases resulting in high morbidity and mortality, making it extremely significant to early diagnosis of ABI. Current methods, which are mainly composed of X-ray computed tomography and magnetic resonance angiography, remain limited in diagnosis of ABI with respect to limited spatial resolution and long scanning times. Here, we reported through-skull fluorescence imaging of mouse cerebral vasculature without craniotomy, utilizing the fluorescence of down-conversion nanoparticles (DCNPs) in the 1.

Photodynamic therapy reduces metastasis of breast cancer by minimizing circulating tumor cells.

Cancer metastasis after traditional surgery introduces a high barrier to therapy efficacy. Photodynamic therapy (PDT) for cancer is based on a photochemical process of photosensitizers that concentrate in tumors and release oxidant species under light excitation to destroy cells. Compared with traditional surgery, PDT provides minimal invasion and targeted therapy.

Ratiometric Raman nanotags enable intraoperative detection of metastatic sentinel lymph node.

Sentinel lymph node (SLN) imaging and biopsy has been advocated as an important technique to evaluate the metastatic status of regional lymph nodes and determine subsequent surgical procedure for many cancers, yet there is no reliable means to provide accurate and rapid diagnosis of metastatic SLN during surgery. Here we develop a new approach, named "Ratiometric Raman dual-nanotag strategy", that using folic acid functionalized targeted and nontargeted gap-enhanced Raman tags (FA-GERTs and Nt-GERTs) to detect metastatic SLN based on Raman imaging combined with classical least square data processing methods. By using this strategy, with built-in self-calibration for signal correction, rather than absolute intensity-dependent signal readout, we realize the visualization and prompt intraoperative diagnosis of metastatic SLN with a high accuracy of 87.

In Vivo Flow Cytometry.

In vivo flow cytometry (IVFC) was first designed to detect circulating cells in a mouse ear. It allows real-time monitoring of cells in peripheral blood with no need to draw blood. The IVFC field has made great progress during the last decade with the development of fluorescence, photoacoustic, and multiphoton microscopy.

Fundamentals of Optical Imaging.

Optical imaging, which possesses noninvasive and high-resolution features for biomedical imaging, has been used to study various biological samples, from in vitro cells, ex vivo tissue, to in vivo imaging of living organism. Furthermore, optical imaging also covers a very wide scope of spatial scale, from submicron sized organelles to macro-scale live biological samples, enabling it a powerful tool for biomedical studies. Before introducing these superior optical imaging methods to researchers, first of all, it is necessary to present the basic concept of light-matter interactions such as absorption, scattering, and fluorescence, which can be used as the imaging contrast and also affect the imaging quality.

Noninvasive and real-time monitoring of Au nanoparticle promoted cancer metastasis using in vivo flow cytometry.

Cancer is the second leading cause of mortality globally, while cancer metastasis, which accounts for about 90% of cancer-related mortality, presents an extremely poor prognosis. Thus, various nanomedicines were designed and synthesized for cancer treatment, but nanomaterials could lead to endothelial leakiness and consequently facilitate intravasation and extravasation of cancer cells to form circulating tumor cells (CTCs), which were regarded as the potential metastatic seeds, possibly accelerating cancer metastasis. Neither possible metastatic sites were observed nor rare CTCs could be measured using common methods at the early stage of cancer metastasis, it is urgent to explore new technology to dynamically monitor nanomedicine promoted cancer metastasis with high sensitivity, which would be beneficial for cancer treatment as well as design and synthesis of nanomedicine.

Rapid ex vivo assessment of cancer prognosis by fluorescence imaging of nucleolus using nitrogen doped carbon dots.

Cancer severely threatens human health currently, promoting the rapid development of cancer treatment strategies. In addition to cancer therapy, assessment of cancer prognosis, which can evaluate the success with treatment and chances of recovery as well as assist to make subsequent therapeutic schedule, is also remarkably indispensable and important. Conventional technologies can't provide rapid and highly-sensitive assessment of cancer prognosis at cytological level.

Near-infrared light excited photodynamic anticancer therapy based on UCNP@AIEgen nanocomposite.

Photodynamic therapy (PDT), a clinically approved cancer treatment strategy, features non-invasiveness, few side-effects, high spatial resolution, The advancement of PDT has been significantly restricted by the penetration depth of the excitation light. Herein, an effective fluorogen, TBD, with aggregation-induced emission characteristics (AIEgen) and high reactive-oxygen-species (ROS) generation efficiency was reported and integrated with a near infrared (NIR) light excitable upconversion nanoparticle (UCNP) to construct NIR light excitable UCNP@TBD nanocomposites. The formed nanocomposite has excellent photostability, good biocompatibility, and efficient ROS generation under NIR light excitation Förster resonance energy transfer (FRET), enabling NIR light excited PDT.

Flexible porphyrin doped polymer optical fibers for rapid and remote detection of trace DNT vapor.

With the rapid growth of anti-terrorist activities worldwide, it becomes an emerging requirement to rapidly and accurately detect hidden explosive threats. However, the safety issue during the explosive material detection, e.g.

Nucleolus-Targeted Photodynamic Anticancer Therapy Using Renal-Clearable Carbon Dots.

Photodynamic therapy (PDT), which utilizes light excited photosensitizers (PSs) to generate reactive oxygen species (ROS) and consequently ablate cancer cells or diseased tissue, has attracted a great deal of attention in the last decades due to its unique advantages. In order to further enhance PDT effect, PSs are functionalized to target specific sub-cellular organelles, but most PSs cannot target nucleolus, which is demonstrated as a more efficient and ideal site for cancer treatment. Here, an effective carbon dots (C-dots) photosensitizer with intrinsic nucleolus-targeting capability, for the first time, is synthesized, characterized, and employed for in vitro and in vivo image-guided photodynamic anticancer therapy with enhanced treatment performance at a low dose of PS and light irradiation.

Recent advances in copper sulphide-based nanoheterostructures.

Due to the high mobility of copper ions in numerous structurally-related phases, copper sulphide (CuS, 0 ≤x≤ 1) has been widely used as a starting template to fabricate various heterostructures via cation exchange. Such nanoheterostructures can possess unique combinations of physical properties that could be useful in diverse applications. Controllable methods of fabricating copper sulphide nanoheterostructures of increasing complexity have been rapidly emerging over the past few years.

In vitro anticancer activity of AIEgens.

Fluorogens with aggregation-induced emission (AIE) characteristics (AIEgens) possess unique optical properties, design flexibility, and multi-functional capabilities and have established their niche as smart materials since their discovery in 2001. In recent years, AIEgens have found varied applications in sensing, imaging, and therapy in biomedical research. In this work, we systematically and comprehensively investigate the in vitro anticancer activity of AIEgens.

Tunable hybridization induced transparency for efficient terahertz sensing.

Hybridization induced transparency (HIT) resulting from the coupling between the material absorption resonance and the artificial structure (metamaterial) resonance provides an effective means of enhancing the sensitivity in the terahertz spectroscopic technique-based sensing applications. However, the application of this method is limited by the versatility to the samples with different volumes, because the samples usually have a refractive index larger than unity and their presence with different thicknesses will lead to a shift of the structure resonance, mismatching the material absorption. In this work, we demonstrate that by using InSb coupled rod structures, whose electromagnetic response in the terahertz band can be easily controlled by using ambient parameters like the temperature or magnetic field, the HIT effect can be easily tuned so that without the needs to change the rod geometry, one can realize efficient terahertz sensing with different sample thickness.

Precise Two-Photon Photodynamic Therapy using an Efficient Photosensitizer with Aggregation-Induced Emission Characteristics.

Two-photon photodynamic therapy (PDT) is able to offer precise 3D manipulation of treatment volumes, providing a target level that is unattainable with current therapeutic techniques. The advancement of this technique is greatly hampered by the availability of photosensitizers with large two-photon absorption (TPA) cross section, high reactive-oxygen-species (ROS) generation efficiency, and bright two-photon fluorescence. Here, an effective photosensitizer with aggregation-induced emission (AIE) characteristics is synthesized, characterized, and encapsulated into an amphiphilic block copolymer to form organic dots for two-photon PDT applications.

In-situ second harmonic generation by cancer cell targeting ZnO nanocrystals to effect photodynamic action in subcellular space.

This paper introduces the concept of in-situ upconversion of deep penetrating near infrared light via second harmonic generation from ZnO nanocrystals delivered into cells to effect photo activated therapies, such as photodynamic therapy, which usually require activation by visible light with limited penetration through biological tissues. We demonstrated this concept by subcellular activation of a photodynamic therapy drug, Chlorin e6, excited within its strong absorption Soret band by the second harmonic (SH) light, generated at 409 nm by ZnO nanocrystals, which were targeted to cancer cells and internalized through the folate-receptor mediated endocytosis. By a combination of theoretical modeling and experimental measurements, we show that SH light, generated in-situ by ZnO nanocrystals significantly contributes to activation of photosensitizer, leading to cell death through both apoptotic and necrotic pathways initiated in the cytoplasm.