Ros-responsive nano-platform for lipid-specific fluorescence imaging of atherosclerosis.

Fluorescent probes that specifically targeting Lipid droplets (LDs) have shown potential in biological imaging. Albeit, their in vivo applications are limited due to the hydrophobicity, low signal-to-noise ratio (SNR) and LDs-specificity. Thus, we designed a novel probe namely MeOND, and a reactive oxygen species (ROS)-responsive nano-platform to improve in vivo LDs-specific imaging. MeOND exhibits a remarkable twisted intramolecular charge transfer (TICT) effect with a strongly enhanced near-infrared emission in low-polarity lipid environment. Also, MeOND demonstrates satisfactory biocompatibility and superior intracellular LDs imaging capabilities. MeOND encapsulated nano-platform (MeOND@PMM) presented favorable water solubility and biocompatibility. MeOND@PMM remains stable in physiological conditions but quickly degrades in the environment of elevated ROS level. The released MeOND could then light up the intracellular LDs in atherosclerotic plaques. The design of the probe and nano-platform is expected to provide a better tool for the scientific research of LDs and LDs-related diseases.

Boosting Alkaline Seawater Oxidation of CoFe-layered Double Hydroxide Nanosheet Array by Cr Doping.

The pursuit of stable and efficient electrocatalysts toward seawater oxidation is of great interest, yet it poses considerable challenges. Herein, the utilization of Cr-doped CoFe-layered double hydroxide nanosheet array is reported on nickel-foam (Cr-CoFe-LDH/NF) as an efficient electrocatalyst for oxygen evolution reaction in alkaline seawater. The Cr-CoFe-LDH/NF catalyst can achieve current densities of 500 and 1000 mA cm -2 with remarkably low overpotentials of only 334 and 369 mV, respectively. Furthermore, it maintains at least 100 h stability when operated at 500 mA cm-2 .

Sn-based electrocatalysts for electrochemical CO2 reduction.

Electrochemical CO2 reduction into value-added chemicals represents an attractive and promising approach to capitalize on the abundant CO2 present in the atmosphere. This reaction, however, is hampered by low energy efficiency and selectivity owing to competition from hydrogen evolution reaction and multiple-electron transfer processes. Therefore, there is a pressing need to develop efficient yet cost-effective electrocatalysts to facilitate practical applications. Sn-based electrocatalysts have gained increasing attention in this active field due to their outstanding merits such as abundance, non-toxicity, and environmental friendliness. This review provides a comprehensive overview of recent advances in Sn-based catalysts for the CO2 reduction reaction (CO2RR), beginning with a brief introduction to the CO2RR mechanism. Subsequently, the CO2RR performance of various Sn-based catalysts with different structures is discussed. The article concludes by addressing the existing challenges and offering personal perspectives on the future prospects in this exciting research area.

A turn-on fluorescent probe for lipid-targeting imaging in human arterial aneurysm and fibrocalcific stenotic aortic valve.

Fluorescence imaging techniques have shown remarkable performance in studying the biological functions of lipid droplets (LDs). However, the biological applications of the commercially available LDs probes suffer from insufficient specificity and low signal/noise ratio (SNR). Herein, we presented a novel near-infrared (NIR) lipid activatable fluorescence probe, namely Me2NND, with extremely low emission in water but significantly enhanced emission in the lipid environment. Me2NND presented good biocompatibility and impressive LDs-specific imaging ability in cells and tissues. Moreover, Me2NND has also shown good photostability and it could efficiently locate the distribution of LDs in human pathological samples of aortic aneurysms and fibrocalcific stenotic aortic valves. This study provided a novel turn-on probe Me2NND and would improve the bio-applications of LDs-specific probes.

Aggregation-induced bioprobe for plasma membrane-specific imaging and photodynamic cancer cell ablation.

Selective labelling of the plasma membrane (PM) by fluorescence imaging techniques enables an intuitive analysis of cell status together with dynamic changes, and therefore is of great value. We herein disclose a novel carbazole-based probe, CPPPy, that shows aggregation-induced emission (AIE) property and is observed to selectively accumulate at the PM of living cells. Benefiting from its good biocompatibility and PM-targeted specificity, CPPPy can light up the PM of cells by high-resolution imaging even at a low concentration of 200 nM. Simultaneously, CPPPy is capable of generating both singlet oxygen and free radical-dominated species upon visible light irradiation, which further induces irreversible growth inhibition and necrocytosis of tumor cells. This study thus provides new insight into the construction of multifunctional fluorescence probes with PM-specific bioimaging and photodynamic therapy.

Aggregation-induced emission fluorescent probes for lipid droplets-specific bioimaging of cells and atherosclerosis plaques.

Visualizing lipid droplets (LDs) using fluorescence imaging is highly desirable for the diagnosis and treatment of atherosclerotic heart diseases. However, the imaging performance of the current commercial lipid probes is unsatisfactory. In this study, we prepared two probes (TTM and MeO-TTM) with aggregation-induced emission (AIE) properties for LD imaging with efficiency. Interestingly, TTM and MeO-TTM showed low emissions in H2O but their emissions were significantly increased in oil. Moreover, TTM and MeO-TTM showed great biocompatibility and intracellular LDs would be specifically illuminated by these probes with good resistance to photobleaching. In addition, TTM and MeO-TTM also exhibited great imaging performance in studying the spatial distribution of LDs in mouse atherosclerotic plaques. This work not only provides a simple tool for studying atherosclerosis but also hopes to enhance the development of fluorescent probes for LDs-specific imaging applications.

A lipid droplet-specific fluorescence probe for atherosclerotic plaque imaging.

The dysregulation of lipid droplets (LDs) is closely related to certain metabolic diseases, while the role of LDs during pathological processes remains mysterious. It would be of great value to monitor the dynamic changes of LDs in a visible way so as to study their biological functions. In this study, we report a LD-specific fluorescence probe TBI for precise LD-targeting imaging in cells and atherosclerotic tissues. TBI exhibited great biocompatibility, remarkable oil-enhanced fluorescence emission, good photostability and impressive intracellular and tissular LD-specific imaging performance. Importantly, TBI could efficiently stain the LDs at a low concentration of 50 nM, and the motion tracking of LDs could be observed via fluorescence imaging. Moreover, TBI could efficiently light up the LD distribution in mouse atherosclerotic plaques with high resolution, which revealed the ultra-structure of atherosclerotic plaques. In conclusion, these results imply that TBI could be a potential tool for investigating the physiological and pathological role of LDs.

A smart probe for simultaneous imaging of the lipid/water microenvironment in atherosclerosis and fatty liver.

A smart lipid droplet specific fluorescent probe (LDs-DM) with dual-emission in water (706 nm) and oil (535 nm) under single-excitation was prepared for revealing the ultra-structure of the aqueous and lipidic microenvironment in living cells, fatty liver tissues and atherosclerotic plaques without fluorescence emission crosstalk. This work is expected to provide inspiration for designing a novel probe with color switching ability.

An intelligent probe with dual-emission in water and oil for lipid droplet specific imaging in human fibrocalcific aortic valvular leaflet.

Lipid droplets (LDs) have been regarded as potential marker for study the pathologic processes and diagnosis of valvular heart disease. While conventional imaging strategy fail to precisely locate LDs in pathological tissues. Herein, a LDs specific probe ECPID with special feature of single-excitation but dual-emission in oil (520 nm) and water (628 nm) was prepared for LDs imaging. ECPID exhibited good biocompatibility, great performance in intracellular and tissular LDs imaging, which would help to reveal the pathologic process of human fibrocalcific aortic valvular leaflet. Our work offers a novel approach for accurate imaging LDs in situ and paves a way to study the pathologic processes of valvular disease.

Direct [4 + 2] Cycloaddition to Isoquinoline-Fused Porphyrins for Near-Infrared Photodynamic Anticancer Agents.

The synthesis of efficient porphyrin-based photosensitizers with intense near-infrared (NIR) absorption is in high demand for photodynamic therapy (PDT) but remains a challenging task. Herein we show the construction of a type of isoquinoline-fused porphyrins 3 and 4 with an impressive NIR-absorbing capacity. In light of the extraordinary singlet oxygen generation capabilities of 3 upon NIR irradiation, the representative nanoparticles (3a-NPs) assembled show excellent tumoricidal behavior with good biocompatibility in the phototherapeutic window (650-850 nm).

A lipid droplet specific fluorescent probe for image-guided photodynamic therapy under hypoxia.

Photodynamic therapy (PDT) is a potential strategy for many superficial, esophageal, intestinal, and bronchial cancer treatments, but its therapeutic effect is limited by a lack of specificity and the hypoxic tumor environment. It is necessary to develop novel photosensitizers (Ps) with organelles targeting and the ability to generate cytotoxic species under light irradiation without the presence of oxygen. Herein, we designed and synthesized a biocompatible fluorescent Ps CPNBD for lipid droplets (LDs) fluorescence (FL) image-guided PDT. CPNBD showed FL quenching in water but FL was significantly turned on by oil with a remarkable FL enhancement compared to that in aqueous solution. Due to its strong lipophilicity (Clog P of 7.96), CPNBD could specifically stain the LDs of human clear cell renal cell carcinoma (ccRCC) tumor cells and tissues with good photostability. Meanwhile, CPNBD could efficiently generate cytotoxic reactive oxygen species under low-power white-light irradiation, which could efficiently damage DNA via a PDT process with great tumor suppression ability in vitro and in vivo. Thus, this work provides a novel strategy for designing LD-targeting Ps with efficient image-guided PDT under the tumor hypoxic environment.

Biomimetic-Coated Nanoplatform with Lipid-Specific Imaging and ROS Responsiveness for Atherosclerosis-Targeted Theranostics.

Atherosclerosis is one of the leading causes of cardiovascular diseases and is triggered by endothelial damage, local lipid cumulation, and inflammation. Despite the conventional medication treatment, nanosized drug carriers have become promising candidates for efficient drug delivery with lower side effects. However, the development of problems in nanocarriers such as drug leakage, accumulating efficiency, and accurate drug release, as well as the specific recognition of atherosclerotic plaques, still needs to be checked. In this study, a lipid-specific fluorophore (LFP) has been designed, which is further packaged with a reactive oxygen species (ROS)-responsive prednisolone (Pred) prodrug copolymer [PMPC-P(MEMA-co-PDMA)] to self-assemble into LFP@PMMP micelles. LFP@PMMP can be further coated with red blood cell (RBC) membrane to obtain surface-biomimetic nanoparticles (RBC/LFP@PMMP), demonstrating prolonged circulation, minimal drug leakage, and better accumulation at the plaques. With ROS responsiveness, RBC/LFP@PMMP can be interrupted at inflammatory atherosclerotic tissue with overexpressed ROS, followed by the dissociation of Pred from the polymer backbone and the release of LFP to combine with the rich lipid in the plaques. An accurate anti-inflammation and lipid-specific fluorescent imaging of atherosclerotic lesions was performed and further proven on ApoE-/- mice; this holds prospective potential for atherosclerosis theranostics.

Turn-on fluorescent probe for lipid droplet specific imaging of fatty liver and atherosclerosis.

Fluorescence imaging plays an important role in researching the biological function of lipid droplets (LDs). However, the short-wave emission, tedious synthesis process and insufficient specificity have significantly limited the applications of commercially available probes. Herein, we have prepared a novel one-step synthesized near-infrared (NIR) fluorescent probe, TNBD, with a very low emission in aqueous solution and the solid state, but a significantly enhanced fluorescence emission is exhibited in oleic acid. Moreover, TNBD exhibited an impressive lipid droplet (LD) specific fluorescence turn-on ability in cells, fatty liver and atherosclerosis (AS) samples with a good biocompatibility and high signal-to-noise ratio. Our study not only establishes a novel LD turn-on fluorescence probe, but also provides a novel way to prepare a NIR LD targeted fluorescence probe.

A bioprosthetic heart valve cross-linked by a non-glutaraldehyde reagent with improved biocompatibility, endothelialization, anti-coagulation and anti-calcification properties.

Valvular heart disease is an important disease that endangers human health and heart valve replacement has become one of the main treatments for patients with severe valvular heart disease. However, the traditional surgical valve replacement (SVR) suffers several drawbacks such as high risk, great trauma and long recovery time, and more than 30% of patients are intolerant to SVR, especially elderly patients. In recent years, with the development of minimally invasive technology, transcatheter heart valve replacement (THVR) as a method of implantation without thoracotomy has become an optimal treatment for severe valvular heart disease due to its advantages of minimal trauma, low risk and fast recovery. Meanwhile, the usage of bioprosthetic heart valves (BHVs) has been enlarged greatly with the rapid development of THVR and the aging population. Most BHVs in clinics are crosslinked by glutaraldehyde (Glut), which shows great mechanical properties and chemical stability. However, some problems such as poor biocompatibility, calcification, coagulation and endothelialization difficulty also need to be solved urgently for Glut-treated BHVs. In this work, a non-Glut treated BHV from 7a-ethyltetrahydro-oxazolo[3,4-c]oxazole (OX-Et) crosslinked porcine pericardium (PP) has been developed. Compared with glutaraldehyde-crosslinked porcine pericardium (Glut-PP), good physical and chemical properties similar to Glut-PP are shown for OX-Et treated porcine pericardium (OX-Et-PP). It is noteworthy that better biocompatibility, endothelialization performance, and anti-coagulant effect as well as the improved anti-calcification property can also be observed for OX-Et-PP in the in vitro and in vivo study, potentially making OX-Et-PP a good candidate in the application of BHVs.

Correction: A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma.

Correction for 'A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma' by Ping Tan et al., Chem. Commun., 2021, DOI: 10.1039/d0cc07336a.

A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma.

A one-step synthesized LD specific fluorescent probe TTIE with high specificity, good photostability and great capacity in generating cytotoxic reactive oxygen species (ROS) under low powered white light irradiation is designed and synthesized for LD specific image-guided photodynamic therapy (PDT) in human clear cell renal cell carcinoma (ccRCC) primary cells and tissues.

ROS Responsive Nanoplatform with Two-Photon AIE Imaging for Atherosclerosis Diagnosis and "Two-Pronged" Therapy.

Atherosclerosis, characterized by endothelial injury, progressive inflammation, and lipid deposition, can cause cardiovascular diseases. Although conventional anti-inflammatory drugs reveal a certain amount of therapeutic effect, more reasonable design on plaque targeting, local anti-inflammation, and lipid removal are still required for comprehensive atherosclerosis therapy. In this work, a theranostic nanoplatform is developed for atherosclerosis recognition and inhibition. A two-photon aggregation-induced emission (AIE) active fluorophore (TP) developed is linked to ß-cyclodextrin (CD) with a ROS responsive bond, which can carry prednisolone (Pred) in its entocoele via supramolecular interaction to build a diagnosis-therapy compound two-photon fluorophore-cyclodextrin/prednisolone complexes (TPCDP). With TPCDP packaged by nanosized micelles based on a ROS sensitive copolymer poly (2-methylthio ethanol methacrylate)-poly (2-methacryloyloxyethyl phosphorylcholine), the TPCDP@PMM can accumulate in atherosclerotic tissue through the damaged vascular endothelium. Activated by the local overexpressed ROS and rich lipid, the micelles are interrupted and TPCDP is further disintegrated with Pred release due to the relatively stronger interaction of lipid with CD, resulting in anti-inflammatory activity and lipid removal for atherosclerosis inhibition. Besides, labeled with the TP, TPCDP@PMM indicates a distinct two-photon AIE imaging on atherosclerosis recognition. The "two-pronged" therapeutic effect and plaque location ability has been confirmed in vivo on ApoE-/- mice, holding TPCDP@PMM a great promise for atherosclerosis theranostics.

pH and singlet oxygen dual-responsive GEM prodrug micelles for efficient combination therapy of chemotherapy and photodynamic therapy.

Nanocarriers have been an important strategy for enhancing the combination therapy of chemotherapy and photodynamic therapy (PDT) (Chem-PDT). However, conventional nanocarriers suffer from the problems of drug leakage in blood and insufficient drug release at target sites. Herein, we have designed a chlorin e6 (Ce6)-loaded GEM prodrug polymer micelle with a singlet oxygen cleavable linker and a pH responsive switch to avoid drug leakage in blood. These Ce6-loaded prodrug micelles possessed a uniform size distribution with a particle size of 78 nm. Meanwhile, the release of Ce6 and GEM was well controlled by acidic pH and laser irradiation. In addition, these micelles showed great acid triggered particle size shrinkage and charge-conversion properties, promoting micelle penetration at tumors and cellular uptake of micelles, which were confirmed by using CLSM of in vitro cell spheres and flow cytometry. Moreover, the in vitro and in vivo1O2 generation ability and antitumor ability of these micelles were impressive. This novel nanocarrier is a potential candidate for efficient Chem-PDT therapy.

Reactive Oxygen Species Responsive Theranostic Nanoplatform for Two-Photon Aggregation-Induced Emission Imaging and Therapy of Acute and Chronic Inflammation.

Inflammation is a protective response to stimuli trauma, which can also lead to severe tissue injury. The existing anti-inflammatory drugs, such as corticosteroids and glucocorticoids, generally exhibit side effects and poor accumulation in inflammatory tissue. Hence, a theranostic nanoplatform with serial reactive oxygen species (ROS) responsiveness and two-photon AIE bioimaging has been constructed for dimensional diagnosis and accurate therapy of inflammation. Prednisolone (Pred) is bridged to a two-photon fluorophore (TP) developed by us via a ROS sensitive bond to form a diagnosis-therapy compound TPP, which is then loaded by the amphipathic polymer PMPC-PMEMA (PMM) through self-assembling into the core-shell structured micelles (TPP@PMM). With a particle size of 57.5 nm, TPP@PMM can realize the accumulation in the inflammatory site via the oedematous tissue and the accurate release of anti-inflammatory drug Pred through the serial response to the local overexpressed ROS. The micellar structure is first interrupted by the ROS triggered hydrophobic-to-hydrophilic conversion of PMEMA, which allows the release of TPP. Then the ROS responsive bond in TPP is subsequently broken, resulting in the accurate delivery of Pred and the inflammation therapy. Furthermore, TPP@PMM can be traced in vivo with a distinct two-photon imaging due to the AIE active fluorophore TP. The theranostic TPP@PMM reveals high-resolution inflammation diagnosis and efficient anti-inflammatory activity owing to the two-photon fluorophore and the serial ROS responsiveness and has been proven to achieve the efficient treatment of acute lung injury, arthritis, and atherosclerosis. Therefore, TPP@PMM holds considerable promise as a potential strategy for acute and chronic inflammation theranostics.

Multi-stimuli responsive polymeric prodrug micelles for combined chemotherapy and photodynamic therapy.

Nowadays, cancer therapy faces severe challenges regarding boosting therapeutic efficiency and reducing the side effects of drugs. To overcome these challenges, herein multifunctional polymeric prodrug micelles combining chemotherapy and photodynamic therapy are put forward; the multifunctional polymeric prodrug micelles are prepared through self-assembly of amphipathic copolymer and photosensitizer Chlorin e6 (Ce6). These therapeutic prodrug micelles have better intracellular uptake and deeper tumor infiltration through charge reversal and smaller size changes, respectively. The polymeric prodrug micelles have fast disassembly and release Ce6 in the case of cathepsin B existence in the lysosome. Under light irradiation at 660 nm, Ce6 can efficiently generate singlet oxygen and accelerate the release of gemcitabine (GEM) by destroying the bis-(alkylthio) alkene functional group, which is the singlet-oxygen responsive linker, to achieve the combination of chemotherapy and photodynamic therapy (PDT). Under light irradiation at 660 nm, the singlet oxygen can also efficiently destroy mitochondrial functions to activate mitochondria apoptosis pathways, including increased reactive oxygen species (ROS) levels and swollen mitochondria. Further, employing 4T1-bearing BALB/c mice as a model, the anticancer effect of the therapeutic prodrug micelles is systematically investigated in vivo. The therapeutic prodrug micelles show an efficient tumor growth inhibition in vivo after light irradiation. Meanwhile, therapeutic prodrug micelles can significantly reduce adverse effects compared with the free drug, exhibiting better biocompatibility. Therefore, this prodrug micelle with a triple sensitivity response and synergistic chemo-photodynamic therapy functions is expected to offer promising applications in efficient antitumor therapy.