Precise visualization and ROS-dependent photodynamic therapy of colorectal cancer with a novel mitochondrial viscosity photosensitive fluorescent probe.

BACKGROUND: Colorectal cancer (CRC) is a prominent global cancer with high mortality rates among human beings. Efficient diagnosis and treatment have always been a challenge for CRC management. Fluorescence guided cancer therapy, which combines diagnosis with therapy into one platform, has brought a new chance for achieving precise cancer theranostics. Among this, photosensitizers, applied in photodynamic therapy (PDT), given the integration of real-time imaging capacity and efficacious treatment feasibility, show great potential to serve as remarkable tools. Although much effort has been put into constructing photosensitizers for locating and destroying CRC cells, it is still in high need to develop novel photosensitizers to attain specific detection and fulfil effective therapy. METHODS: Probe HTI was rational synthesized for the diagnosis and treatment of CRC. Spectrometric determination was carried out first, followed by the 1O2 generation ability test. Then, HTI was displayed in distinguishing CRC cells from normal cells Further, the PDT effect of the photosensitizer was studied in vitro. Additionally, HTI was used in CRC BALB/c nude mice model to validate its viscosity labelling and tumor suppression characteristics. RESULTS: We successfully fabricated a mitochondrial targeting probe, HTI, together with remarkable viscosity sensitivity, ultralow background interference, and excellent 1O2 generation capacity. HTI was favorably applied to the viscosity detection, displaying a 11-fold fluorescent intensity enhancement in solvents from 1.57 cp to 2043 cp. Then, it was demonstrated that HTI could distinguish CRC cells from normal cells upon the difference in mitochondrial viscosity. Moreover, HTI was qualified for producing 1O2 with high efficiency in cells, supported by the sparkling signals of DCFH after incubation with HTI under light irradiation. More importantly, the viscosity labelling and tumor suppression performance in CRC CDX model was determined, enriching the multifunctional validation of HTI in vivo. CONCLUSIONS: In this study, HTI was demonstrated to show a sensitive response to mitochondrial viscosity and possess a high 1O2 generation capacity. Both in vitro cell imaging and in vivo tumor treatment trials proved that HTI was effectively served as a robust scaffold for tumor labeling and CRC cells clearance. This breakthrough discovery held immense potential for advancing the early diagnosis and management of CRC through PDT. By leveraging HTI's properties, medical professionals could benefit from improved diagnostic accuracy and targeted treatment in CRC management, ultimately leading to enhanced patient outcomes.

Fidelity-oriented fluorescence imaging probes for beta-galactosidase: From accurate diagnosis to precise treatment.

Beta-galactosidase (ß-gal), a typical glycosidase catalyzing the hydrolysis of glycosidic bonds, is regarded as a vital biomarker for cell senescence and cancer occurrence. Given the advantages of high spatiotemporal resolution, high sensitivity, non-invasiveness, and being free of ionizing radiations, fluorescent imaging technology provides an excellent choice for in vivo imaging of ß-gal. In this review, we detail the representative biotech advances of fluorescence imaging probes for ß-gal bearing diverse fidelity-oriented improvements to elucidate their future potential in preclinical research and clinical application. Next, we propose the comprehensive design strategies of imaging probes for ß-gal with respect of high fidelity. Considering the systematic implementation approaches, a range of high-fidelity imaging-guided theragnostic are adopted for the individual ß-gal-associated biological scenarios. Finally, current challenges and future trends are proposed to promote the next development of imaging agents for individual and specific application scenarios.

Functional insights from targeted imaging BACE1: the first near-infrared fluorescent probe for Alzheimer's disease diagnosis.

BACKGROUND: ß-Secretase (BACE1) is the vital enzyme in the pathogenic processes of Alzheimer's disease (AD). However, the development of a powerful tool with sensitivity for BACE1 determination in vivo is a challenge. METHODS: A novel NIR fluorescent probe HBAE was synthetized from 2-hydroxy-3-methylbenzaldehyde and 2-amino-benzenethiol by 5 steps. The fluorescence mechanism in the ESIPT systems of HBAE probe was insighted with time-dependent density functional theory (TD-DFT) at the TDPBE0 level with the def2-TZVP approach. The corresponding docking between HBAE and BACE1 (PDB: 5I3Y) was performed through the ducking method by DOCK6.8. Then the BBB permeability of HBAE is verified by transwell orifice plate. 22-month-old male AD-model (5XFAD) mice and age-matched wild-type mice were employed to observe the brain kinetics by intravenous injection. Finally, Immunohistochemistry was performed on the AD brain section to reveal the levels of BACE1 in hippocampus and cortex areas and other regions in AD mice through the brain tissue slices by HBAE. RESULTS: The NIR fluorescent probe HBAE was successfully applied in imaging BACE1 in AD model mice. The capability of HBAE in reflecting different level of BACE1 was performed by the specific imaging of the hippocampus region. CONCLUSIONS: We reported the first ESIPT near-infrared fluorescence probe HBAE for monitoring endogenous BACE1 in the AD live model mice, thus offering a versatile chemical tool for visualizing in the pathological processes of AD live brains. Remarkably, high resolution images showed the localization of red fluorescence stains in hippocampus of the AD brain. This study provides a promising way for functional insights from protein BACE1 in vivo.

NIR-I Dye-Based Probe: A New Window for Bimodal Tumor Theranostics.

Near-infrared (NIR, 650-1700 nm) bioimaging has emerged as a powerful strategy in tumor diagnosis. In particular, NIR-I fluorescence imaging (650-950 nm) has drawn more attention, benefiting from the high quantum yield and good biocompatibility. Since their biomedical applications are slightly limited by their relatively low penetration depth, NIR-I fluorescence imaging probes have been under extensive development in recent years. This review summarizes the particular application of the NIR-I fluorescent dye-contained bimodal probes, with emphasis on related nanoprobes. These probes have enabled us to overcome the drawbacks of individual imaging modalities as well as achieve synergistic imaging. Meanwhile, the application of these NIR-I fluorescence-based bimodal probes for cancer theranostics is highlighted.

Highly selective and sensitive detection of arsenite ions(III) using a novel tetraphenylimidazole-based probe.

More than 200 million people in the world are exposed to areas where the arsenic concentration exceeds the limit allowed for living species, which urges researchers to develop low-cost methods for the selective and fast detection of arsenic ions in environmental samples. Herein, we report a novel tetraphenylimidazole-based probe (TBAB) functionalized with a Schiff base for sensing and detecting arsenic ions in aqueous media. Upon the addition of arsenic ions, an obvious fluorescence change from faint yellow to green was observed visible to the naked eye. The probe can detect arsenic selectively in the presence of interfering substances, with a lower detection limit than 0.7 ppb, a value which is far lower than the limit set by the WHO. A detailed mechanism revealed that the chelation of TBAB with arsenic activated the AIE characteristic, leading to the enhanced fluorescence, which was verified by Job's plot experiment and HRMS. Its practicality was further validated by the analysis of real water samples, demonstrating its potential application for on-site detection and biological application.

Construction and theoretical insights into the ESIPT fluorescent probe for imaging formaldehyde in vitro and in vivo.

We report the first ESIPT-based probe ABTB, for the highly sensitive and selective imaging of formaldehyde (FA). The various theoretical calculations have been systematically performed, and clearly unravel the lighting mechanism of the fluorescent probe for FA. Additionally, the probe was successfully applied in monitoring endogenous FA in the brain of AD mice.

Wash-free 3D imaging and detection of glioma with a novel neuropotential targeted AIE probe.

We herein developed a novel tetraarylimidazole-based AIE probe TPIG-NP to selectively image and quantitatively detect glioma. Due to the distinct negatively charged glioma cells, TPIG-NP with an opposite charge could achieve wash-free imaging of glioma cells and 3D multicellular spheroids.

A novel self-assembled nanoprobe for the detection of aluminum ions in real water samples and living cells.

Aluminum ions, as a kind of non-essential element, show a negative impact on plants growth and contribute to diseases caused by nervous breakdown like Alzheimer's disease and Parkinson's disease. Hence, the detection of Al3+ in environment and human body is of great significance and valuableness. Herein, a N-H-type excited-state intramolecular proton transfer (ESIPT) based self-assemble nanoprobe has been designed and synthesized for the detection of Al3+. Owing to phthalandione and tosyl group, probe ABTTA could self-assemble into nanoparticles with nearly no fluorescence. However, ABTTA would be further aggregated by Al3+ ions in aqueous solution which results in enhanced fluorescence (peaking at 555 nm). Based on this principle, a novel analytical method for detection of Al3+ was established with a limit of detection of 50 nM, which was much better than most of reported probes. Moreover, the nanoprobe with excellent water solubility was successfully applied for the detection of Al3+ in real water sample with satisfactory measurement accuracy. Benefited from the favorable water solubility, the nanoprobe was further utilized to the detection of Al3+ in human cancer samples, demonstrating its potential application for biological imaging.

Applications of Nanoparticles Probes for Prostate Cancer Imaging and Therapy.

Prostate cancer (PCa) is the most common type of cancer in men with high morbidity and mortality. However, the current treatment with drugs often leads to chemotherapy resistance. It is known that the multi-disciplines research on molecular imaging is very helpful for early diagnosing, staging, restaging and precise treatment of PCa. In the past decades, the tumor-specific targeted drugs were developed for the clinic to treat prostate cancer. Among them, the emerging nanotechnology has brought about many exciting novel diagnosis and treatments systems for PCa. Nanotechnology can greatly enhance the treatment activity of PCa and provide novel theranostics platform by utilizing the unique physical/chemical properties, targeting strategy, or by loading with imaging/therapeutic agents. Herein, this chapter focuses on state-of-art advances in imaging and diagnosing PCa with nanomaterials and highlights the approaches used for functionalization of the targeted biomolecules, and in the treatment for various aspects of PCa with multifunctional nanoparticles, nanoplatforms and nanodelivery system.

Fluorescent probes for the detection of magnesium ions (Mg2+): from design to application.

Magnesium ions (Mg2+) play essential roles in various physiological and pathological processes, its abnormal homeostasis in cells is related to many diseases, such as diabetes, neuromuscular disorders, hypertension and other cardiovascular disorders. Investigation on the regulation of magnesium in cellular processes has attracted considerable interest in the past several decades. Among those reported strategies, fluorescent imaging technology has become a powerful and cost-effective tool for the real-time monitoring of magnesium distribution, uptake and trafficking, due to its superior features of high sensitivity and non-invasiveness, as well as excellent spatial and temporal fidelity. Herein, we critically summarize the progresses in the intracellular magnesium detection with fluorescent imaging probes. Our discussion focuses on the recent contributions concerning fluorescent imaging probes for mapping magnesium in biological processes. All the candidates are organized according to their acceptor structures. The sensing mechanisms of fluorescent probes are also highly taken into account. Challenges, trends and prospects of fluorescent imaging technology in magnesium detection are also set forth.

Advances of Molecular Imaging for Monitoring the Anatomical and Functional Architecture of the Olfactory System.

The olfactory system of organisms serves as a genetically and anatomically model for studying how sensory input can be translated into behavior output. Some neurologic diseases are considered to be related to olfactory disturbance, especially Alzheimer's disease, Parkinson's disease, multiple sclerosis, and so forth. However, it is still unclear how the olfactory system affects disease generation processes and olfaction delivery processes. Molecular imaging, a modern multidisciplinary technology, can provide valid tools for the early detection and characterization of diseases, evaluation of treatment, and study of biological processes in living subjects, since molecular imaging applies specific molecular probes as a novel approach to produce special data to study biological processes in cellular and subcellular levels. Recently, molecular imaging plays a key role in studying the activation of olfactory system, thus it could help to prevent or delay some diseases. Herein, we present a comprehensive review on the research progress of the imaging probes for visualizing olfactory system, which is classified on different imaging modalities, including PET, MRI, and optical imaging. Additionally, the probes' design, sensing mechanism, and biological application are discussed. Finally, we provide an outlook for future studies in this field.

Upconversion nanocomposites for photo-based cancer theranostics.

Lanthanide ion doped upconversion nanoparticles (UCNPs) are known to be able to convert long-wavelength excitation light (usually 980 nm) into high-energy ultraviolet (UV) or visible emissions, and they have attracted significant attention because of their distinct photochemical properties including sharp emission bands, low autofluorescence, high tissue penetration depth, inertness to ambient interference and minimal photodamage to tissues. Until now, UCNPs have shown great potential in various realms including bioimaging, biosensing and biomedical applications. Especially in recent years, UCNP based nanocomposites have been found to be promising tools for multi-modal imaging and low-invasive photo-based therapy of tumors. In this review, we summarize the recent achievement and progress of UCNP based multifunctional nanoplatforms for bioimaging and cancer phototheranostics, including photodynamic therapy (PDT) and photothermal therapy (PTT). Furthermore, some emerging trends, future directions as well as challenges in this rapidly growing field are discussed.

A water-soluble ESIPT fluorescent probe with high quantum yield and red emission for ratiometric detection of inorganic and organic palladium.

A novel fluorescent probe with a high quantum yield (0.41), large Stokes shifts (255 nm), and red emission (635 nm) was designed to detect all typical oxidation states of palladium species (0, +2, +4) by palladium-mediated terminal propargyl ethers cleavage reaction in water solution without any organic media. The probe showed a high selectivity and excellent sensitivity for palladium species, with a detection as low as 57 nM (6.2 µg L(-1)).