Aggregation-Induced Emission (AIE), Life and Health

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health

Emerging contrast agents for multispectral optoacoustic imaging and their biomedical applications

Optoacoustic imaging is a hybrid biomedical imaging modality which collects ultrasound waves generated via photoexciting contrast agents in tissues and produces images of high resolution and penetration depth. As a functional optoacoustic imaging technique, multispectral optoacoustic imaging, which can discriminate optoacoustic signals from different contrast agents by illuminating samples with multi-wavelength lasers and then processing the collected data with specific algorithms, assists in the identification of a specific contrast agent in target tissues and enables simultaneous molecular and physiological imaging. Moreover, multispectral optoacoustic imaging can also generate threedimensional images for biological tissues/samples with high resolution and thus holds great potential in biomedical applications. Contrast agents play essential roles in optoacoustic imaging, and they have been widely explored and applied as probes and sensors in recent years, leading to the emergence of a variety of new contrast agents. In this review, we aim to summarize the latest advances in emerging contrast agents, especially the activatable ones which can respond to specific biological stimuli, as well as their preclinical and clinical applications. We highlight their design strategies, discuss the challenges and prospects in multispectral optoacoustic imaging, and outline the possibility of applying it in clinical translation and public health services using synthetic contrast agents.Agency for Science, Technology and Research (A*STAR)National Research Foundation (NRF)Submitted/Accepted versionThis work was supported by the National Natural Science Foundation of China (21788102), the Fund of Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates (2019B030301003), the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081), and the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03)

A multifunctional nanoaggregate‐based system for detection of rheumatoid arthritis via Optoacoustic/NIR‐II fluorescent imaging and therapy via inhibiting JAK‐STAT/NF‐κB/NLRP3 pathways

Abstract Rheumatoid arthritis (RA) is a debilitating autoimmune disease that causes chronic pain and serious complications, presenting a significant challenge to treat. Promising approaches for treating RA involve signaling pathways modulation and targeted therapy. To this end, a multifunctional nanosystem, TPC‐U@HAT, has been designed for RA therapy, featuring multitargeting, dual‐stimuli response, and on‐demand drug release capabilities. TPC‐U@HAT is composed of a probe/prodrug TPC, a JAK1 kinase inhibitor upadacitinib, and the drug carrier HAT. TPC is composed of an aggregation‐induced emission (AIE)‐active NIR‐II chromophore TPY and an NF‐κB/NLRP3 inhibitor caffeic acid phenethyl ester (CAPE), connected via boronic ester bond which serves as the reactive‐oxygen‐species‐responsive linker. The carrier, HAT, is created by grafting bone‐targeting alendronate and hydrophobic tocopheryl succinate onto hyaluronic acid chains, which can encapsulate TPC and upadacitinib to form TPC‐U@HAT. Upon intravenous injection into mice, TPC‐U@HAT accumulates at inflamed lesions of RA through both active and passive targeting, and the overexpressed hyaluronidase and H2O2 therein cleave the hyaluronic acid polymer chains and boronate bonds, respectively. This generates an AIE‐active chromophore for detection and therapeutic evaluation of RA via both optoacoustic imaging and NIR‐II fluorescent imaging and concomitantly releases CAPE and upadacitinib to exert efficacious therapy by inhibiting NF‐κB/NLRP3 and JAK‐STAT pathways

A H₂O₂-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-II fluorescent imaging

Developing high-quality NIR-II fluorophores (emission in 1000-1700 nm) for in vivo imaging is of great significance. Benzothiadiazole-core fluorophores are an important class of NIR-II dyes, yet ongoing limitations such as aggregation-caused quenching in aqueous milieu and non-activatable response are still major obstacles for their biological applications. Here, we devise an activatable nanoprobe to address these limitations. A molecular probe named BTPE-NO2 is synthesized by linking a benzothiadiazole core with two tetraphenylene groups serving as hydrophobic molecular rotors, followed by incorporating two nitrophenyloxoacetamide units at both ends of the core as recognition moieties and fluorescence quenchers. An FDA-approved amphiphilic polymer Pluronic F127 is then employed to encapsulate the molecular BTPE-NO2 to render the nanoprobe BTPE-NO2@F127. The pathological levels of H2O2 in the disease sites cleave the nitrophenyloxoacetamide groups and activate the probe, thereby generating strong fluorescent emission (950~1200 nm) and ultrasound signal for multi-mode imaging of inflammatory diseases. The nanoprobe can therefore function as a robust tool for detecting and imaging the disease sites with NIR-II fluorescent and multispectral optoacoustic tomography (MSOT) imaging. Moreover, the three-dimensional MSOT images can be obtained for visualizing and locating the disease foci.Agency for Science, Technology and Research (A*STAR)National Research Foundation (NRF)Published versionThis work was supported by the National Natural Science Foundation of China (No. 21788102 to S.W. and No. 21875069 to F.Z.), the Natural Science Foundation of Guangdong Province (No. 2016A030312002 to S.W.), and the Fund of Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates (No. 2019B030301003 to S.W.). The work was also supported by the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (No. A20E5c0081 to Y.Z.) and the Singapore National Research Foundation Investigatorship (No. NRF-NRFI2018- 03 to Y.Z.)

Conjugation with Betaine: A Facile and Effective Approach to Significant Improvement of Gene Delivery Properties of PEI

Herein, we developed a new gene delivery vector by grafting a betaine monomer (<i>N</i>,<i>N</i>-dimethyl­(acrylamidopropyl)­ammonium propane sulfonate, DMAAPS) onto 25 KDa polyethylenimine (PEI 25K) via the Michael addition reaction. The graft ratio for betaine on PEI polymer could be readily controlled, and in this study three PEI-betaine conjugates PEI-DMAAPS_23%, PEI-DMAAPS_55%, and PEI-DMAAPS_95% were prepared with their graft ratios of 23, 55, and 95%, respectively. The PEI-betaine conjugates exhibited much lower protein adsorption and cytotoxicities compared with PEI 25K, and they also showed little or no hemolytic effect. Moreover, the PEI-betaine conjugates display satisfactory DNA condensation capability; and in the absence and presence of serum, PEI-DMAAPS_23%/pEGFP and PEI-DMAAPS_55%/pEGFP complexes exhibited remarkable gene transfection efficiencies determined by flow cytometry, which are in general several times higher than that of PEI 25K. With these favorable properties, the PEI-betaine conjugates hold great potential for use as efficient gene delivery vectors. This study suggests that the betaine monomer may serve as a biocompatible modifying agent and this facile strategy may provide a facile and effective way for constructing some other biocompatible materials

Dual-Targeting Nanosystem for Enhancing Photodynamic Therapy Efficiency

Photodynamic therapy (PDT) has been recognized as a valuable treatment option for localized cancers. Herein, we demonstrate a cellular and subcellular targeted strategy to facilitate PDT efficacy. The PDT system was fabricated by incorporating a cationic porphyrin derivative (MitoTPP) onto the polyethylene glycol (PEG)-functionalized and folic acid-modified nanographene oxide (NGO). For this PDT system, NGO serves as the carrier for MitoTPP as well as the quencher for MitoTPP’s fluorescence and singlet oxygen (¹O₂) generation. Attaching a hydrophobic cation to the photosensitizer ensures its release from NGO at lower pH values as well as its mitochondria-targeting capability. Laser confocal microscope experiments demonstrate that this dual-targeted nanosystem could preferably enter the cancer cells overexpressed with folate receptor, and release its cargo MitoTPP, which subsequently accumulates in mitochondria. Upon light irradiation, the released MitoTPP molecules generate singlet oxygen and cause oxidant damage to the mitochondria. Cell viability assays suggest that the dual-targeted nanohybrids exhibit much higher cytotoxicity toward the FR-positive cells

Polymer Micelle with pH-Triggered Hydrophobic–Hydrophilic Transition and De-Cross-Linking Process in the Core and Its Application for Targeted Anticancer Drug Delivery

In this study, an novel amphiphilic block copolymer P­[PEGMA-<i>b</i>-(DEMA-<i>co</i>-APMA)]-FA and its cross-linker uracil-(CH₂)₆-uracil (U-(CH₂)₆-U) were synthesized and used as the targeted and pH-responsive nanocarriers for anticancer drug delivery. The hydrophobic block of the copolymer contains adenine (A) and tertiary amine moieties and the hydrophilic block is terminated with a targeting ligand folic acid (FA). Under neutral pH, the hydrophobic chain segments of the copolymer are cross-linked by U-(CH₂)₆-U through the A-U nucleobase pairing based on complementary multiple hydrogen bonding, and the copolymer forms stable micelles with their mean diameter of around 170 nm in water. While under acidic pH, the micelles dissociate as a result of protonation of tertiary amines and disruption of the A-U nucleobase pairing. Flow cytometry and fluorescent microscope observation show that, when loaded with an anticancer drug DOX, the micelles can preferably enter folate receptor (FR)-positive cancer cells and kill the cells via intracellular release of the anticancer drug. Cytotoxicity tests (MTT tests) indicate that the micelles with FA on their surfaces exhibit higher cytotoxicity toward FR-positive cells than those without FA. This study provides useful insights on designing and improving the applicability of copolymer micelles for other targeted drug delivery systems