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A kind of functional BHV material has been exploited which exhibits superior anti-inflammation, improved anti-coagulation, minimal calcification and promoted proliferation of endothelial cells.

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.

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.

AIE fluorophores have been developed as bioimaging probes due to their strong brightness at high concentration and increase of the photostability to promote highly recognizable cellular signaling. However, conventional AIE fluorescent probes for bioimaging just solely lighten the cells or tissues, suffering from the limitation of satisfying the requirement of disease diagnosis. Herein, we report an AIE-active bioprobe (TPP-Tba) for linear fluorescence response and qualitative detection of hydrogen peroxide (H2O2) and viscosity with a wide detection range and a low detection limit. TPP-Tba displays an impressive ability of distinguishing normal cells and pathological cells. Furthermore, fatty liver tissue can also be efficiently distinguished from normal liver tissue, attributed to the great H2O2 and viscosity dual-response as well as the specific targeting to mitochondria by TPP-Tba. Given the high sensitivity for H2O2 and viscosity, great biocompatibility, high specificity to mitochondria, and impressive ability of distinguishing normal tissue and pathological tissue, we envisage that this novel TPP-Tba probe would open a new window for designing novel bioprobes for disease diagnosis.

Cardiovascular diseases have become the leading cause of death worldwide. The increasing burden of cardiovascular diseases has become a major public health problem and how to carry out efficient and reliable treatment of cardiovascular diseases has become an urgent global problem to be solved. Recently, implantable biomaterials and devices, especially minimally invasive interventional ones, such as vascular stents, artificial heart valves, bioprosthetic cardiac occluders, artificial graft cardiac patches, atrial shunts, and injectable hydrogels against heart failure, have become the most effective means in the treatment of cardiovascular diseases. Herein, an overview of the challenges and research frontier of innovative biomaterials and devices for the treatment of cardiovascular diseases is provided, and their future development directions are discussed.

Nowadays, photodynamic therapy (PDT) has become an effective method for cancer therapy. However, there are still some drawbacks with common photosensitizers including poor photostability, nonspecific targeting, poor tissue penetration depth, low PDT efficiency, etc. Therefore, the development of high-performance photosensitizers is highly desirable. In this study, we design an aggregation-induced emission (AIE) photosensitizer TBBP based on a D–π–A skeleton. This photosensitizer TBBP exhibits strong aggregation-induced emission, large two-photon absorption cross-section, high specificity to mitochondria, deep tissue imaging with a penetration depth up to 150 μm and excellent biocompatibility, showing great potential as a bioprobe in two-photon cell and tissue bioimaging. Furthermore, a higher PDT efficiency than the most commonly used commercial photosensitizer Ce6 has been shown for TBBP owing to the efficient 1O2 generation, the high 1O2 quantum yield and the enhanced endocytosis. The two-photon cell and deep tissue bioimaging and highly efficient mitochondria-targeted photodynamic therapy endow this AIE fluorophore TBBP with great potential in clinical applications.

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.

Atherosclerosis, as a life-threatening cardiovascular disease with chronic inflammation and abnormal lipid enrichment, is often difficult to treat timely due to the lack of obvious symptoms. In this work, a theranostic nanoplatform is constructed for the noninvasive in vivo diagnosis, plaque-formation inhibition, and the lesion reversal of atherosclerosis. A three-in-one therapeutic complex is constructed and packaged along with a polymeric photoacoustic probe into nanoparticles named as PLCDP@PMH, which indicates an atherosclerosis-targeting accumulation and a reactive oxygen species (ROS)/matrix metalloproteinase (MMP) dual-responsive degradation. The photoacoustic probe suggests a lesion-specific imaging on atherosclerotic mice with an accurate and distinct recognition of plaques. At the same time, the three-in-one complex performs an integrated lipid management through the inhibition of macrophages M1-polarization, liver X receptor (LXR)-mediated up-regulation of ATP-binding cassette transporter A1/G1 (ABCA1/G1) and the cyclodextrin-assisted lipid dissolution, which lead to the reduced lipid uptake, enhanced lipid efflux, and actuated lipid removal. The in vivo evaluations reveal that PLCDP@PMH can suppress the lesion progression and further reverse the formed plaques under a diet without high fat. Hence, PLCDP@PMH provides a candidate for the theranostics of early-stage atherosclerosis and delivers an impressive potential on the reversal of formed atherosclerotic lesions.

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.

Atherosclerosis, which is triggered by endothelial damage, progressive local inflammation and excessive lipid accumulation, is one of the most common cardiovascular diseases in recent years. Drug delivery systems have shown great potential for the accurate diagnosis and effective treatment of early atherosclerosis, but are accompanied by disadvantages such as poor stability, lack of active targeting and non-specific recognition capabilities, which still need to be further developed. In our work, a multifunctional nanoparticle (LFP/PCDPD) with reactive oxygen species (ROS) responsive drug release, lipid removal, and lipid-specific AIE fluorescence imaging was constructed. Cyclodextrin structure with lipid removal function and PMEMA blocks with ROS-response-mediated hydrophobic to hydrophilic conversion were simultaneously introduced into the structure of LFP/PCDPD to load the anti-inflammatory drug prednisolone (Pred) and lipid-specific AIEgen (LFP). The active targeting function of LFP/PCDPD was conferred by the high affinity of dextran to the vascular adhesion molecule-1 (VCAM-1) and CD44 receptor on the surface of broken endothelial cells. After intravenous injection into ApoE

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.

Theranostic nanoplatforms haev been proven to be a feasible strategy against cancer for convenient diagnosis, efficient drug release, and reduced side effects. However, the drug leakage during blood circulation, poor cellular uptake of drug-loaded nanoparticles, and insufficient drug release still remain to be overcome. Herein, a hierarchical pH and reactive oxygen species (ROS)-responsive nanoplatform is constructed labeling with a two-photon fluorophore developed by us, aiming for a programmed drug delivery and an intensive two-photon bioimaging. With the capecitabine (Cap) conjugated, the prodrug polymer PMPC-b-P[MPA(Cap)-co-TPMA]-PAEMA (PMMTAb-Cap) can be self-assembled into the core-shell structured micelles, which can stay stable in the blood stream. Once the micelles accumulate at the tumor tissue, the outside PMPC shell can be desquamated while the inner PAEMA become hydrophilic and electropositive under the acidic extracellular tumor microenvironment, leading to a shrunken micellar size for the better penetration along with enhanced endocytosis. After cellular internalization, the overexpressed intracellular ROS can eventually trigger the drug delivery for an accurate tumor therapy, which is confirmed by the in vivo antitumor experiments. Furthermore, the in vivo micellar biodistribution can be traced by a deep tissue imaging up to 150 μm because of the aggregation-induced emission active two-photon fluorophore. As a theranostic nanoplatform with two-photon bioimaging and hierarchical responsiveness, these PMMTAb-Cap micelles can be a potential candidate for tumor theranostical applications.

Nanodrug carriers with fluorescence radiation are widely used in cancer diagnosis and therapy due to their real-time imaging, less side effect, better drug utilization as well as the good bioimaging ability. However, traditional nanocarriers still suffer from unexpectable drug leakage, unsatisfactory tumor-targeted drug delivery and shallow imaging depth, which limit their further application in cancer theranostics. In this study, an integrated nanoplatform is constructed by polymeric prodrug micelles with two-photon and aggregation-induced emission bioimaging, charge reversal and drug delivery triggered by acidic pH. The prodrug micelles can be self-assembled by the TP-PEI (DA/DOX)-PEG prodrug polymer, which consists of the two-photon fluorophore (TP), dimethylmaleic anhydride (DA) grafted polyethyleneimine (PEI) and polyethylene glycol (PEG). The PEG segment, DOX and DA are bridged to polymer by acid cleavable bonds, which provides the micelles a ‘stealth’ property and a satisfactory stability during blood circulation, while the outside PEG segment is abandoned along with the DA protection in the tumor acidic microenvironment, thus leading to charge reversal-mediated accelerated endocytosis and tumor-targeted drug delivery. The great antitumor efficacy and reduced side effect of these pH-sensitive prodrug micelles are confirmed by antitumor assays in vitro and in vivo. Meanwhile, these micelles exhibited great deep-tissue two-photon bioimaging ability up to 150 μm in depth. The great antitumor efficacy, reduced side effect and deep two-photon tissue imaging make the TP-PEI (DA/DOX)-PEG prodrug micelles would be an efficient strategy for theranostic nanoplatform in cancer treatment.

Intelligent polymeric micelles provide great potential for accurate cancer theranostics. Herein, gemcitabine (GEM)-conjugated redox-responsive prodrug micelles based on a pH-responsive charge-conventional PMPC-b-P (DEMA-co-SS-GEM-co-TPMA) copolymer and a two-photon absorbing aggregation-induced emission (AIE) fluorescence probe have been developed for lysosome-targeted drug release and bioimaging. The multifunctional copolymer has been synthesized via RAFT polymerization, and GEM is conjugated to the copolymer via GSH-cleavable disulfide bonds. These GEM-conjugated micelles exhibit great pH responsiveness at pH 5.0, while being stable at pH 6.0. GSH-triggered drug release can be observed with the GSH concentration increased from 0 to 10 mM. Moreover, the high-quality AIE-active two-photon imaging is confirmed by cell and deep-tissue imaging. More importantly, the distribution of these nanocarriers can be traced because of the AIE feature of the micelles. Along with good in vitro and in vivo tumor-suppression ability and significantly reduced side effects, this smart two-photon AIE micelle would be a potential candidate for cancer diagnosis and therapy.

In recent years, photodynamic therapy (PDT) has drawn much attention as a noninvasive and safe cancer therapy method due to its fine controllability, good selectivity, low systemic toxicity, and minimal drug resistance in contrast to the conventional methods (for example, chemotherapy, radiotherapy, and surgery). However, some drawbacks still remain for the current organic photosensitizers such as low singlet oxygen (1O2) quantum yield, poor photostability, inability of absorption in the near-infrared (NIR) region, short excitation wavelength, and limited action radius of singlet oxygen, which will strongly limit the PDT treatment efficiency. As a consequence, the development of efficient photosensitizers with high singlet oxygen quantum yield, strong fluorescent emission in the aggregated state, excellent photostability, NIR excitation wavelength ranging in the biological transparency window, and highly specific targeting to mitochondria is still in great demand for the enhancement of PDT treatment efficiency. In this study, two new two-photon AIEgens TPPM and TTPM based on a rigid D-π-A skeleton have been designed and synthesized. Both AIEgens TPPM and TTPM show strong aggregation-induced emission (AIE) with the emission enhancement up to 290-folds, large two-photon absorption with the two-photon absorption cross section up to 477 MG, and highly specific targeting to mitochondria in living cells with good biocompatibility. They can serve as two-photon bioprobes for the cell and deep tissue bioimaging with a penetration depth up to 150 μm. Furthermore, high 1O2 generation efficiency with high 1O2 quantum yield under white light irradiation has been found for both TPPM and TTPM and high PDT efficiency to HeLa cells under white light irradiation has also been proven. To the best of our knowledge, AIEgens in this work constitute one of the strongest emission enhancements and one of the highest 1O2 generation efficiencies in the reported organic AIEgens so far. The great AIE feature, large two-photon absorption, high specificity to mitochondria in living cells, and high PDT efficiency to living cells as well as excellent photostability and biocompatibility of these novel AIEgens TPPM and TTPM reveal great potential in clinical applications of two-photon cell and tissue bioimaging and image-guided and mitochondria-targeted photodynamic cancer therapy.

Nanoparticles armed with chemotherapy drug and fluorescence probe have become an effective anticancer strategy for their advantages in cancer diagnosis and treatment. However, fluorophore for diagnostic medicine with deep penetration depth and high resolution are still very rare, while rational designs are also required to improve the tumor retention and target-site drug delivery. Herein, a two-photon fluorophore with aggregation-induced emission and large two-photon absorption cross-section has been designed for two-photon bioimaging, and a novel theranostic nanoplatform is also constructed based on doxorubicin and the two-photon fluorophore conjugated copolymer, P(TPMA-co-AEMA)-PEI(DA)-Blink-PEG (PAEEBlink-DA). The micelles maintain a “stealth” property during blood circulation and is activated in the acidic tumor microenvironment, which triggers the charge-conversion and results in enhanced micellar internalization. Meanwhile, PAEMA chains can convert from hydrophobicity to hydrophilicity with accelerated drug release and particle size expansion. The enlarged particle size would potentially extend the retention time of these micelles. Moreover, a great AIE active two-photon bioimaging with tissue penetration depth up to 150 µm is observed and the in vivo biodistribution of nanoparticles can be traced. The in vivo antitumor results further indicate the obvious reduction of adverse effect and enhanced treatment effect of these micelles, proving that these PAEEBlink-DA micelles would be a potential candidate for tumor theranostic applications.

Functional drug carriers with simultaneous effective delivery of therapeutic agents to target sites and great imaging ability have attracted great attention in nanomedicine research. In this work, we developed a multi-functional polymeric micelle based on a folate (FA)-modified triblock copolymer P(TPF-co-Ibup)–PAEMA–PPEG@FA as a smart drug delivery system with anti-tumor and anti-inflammatory abilities, charge conversion and FA-mediated enhanced cellular uptake, and AIE active two-photon bioimaging. Anticancer drug curcumin (CUR) was encapsulated with a high loading capacity and these CUR-loaded micelles exhibited great stability with a negatively charged surface in a physiological environment. However, the acidic tumor environment would rapidly trigger charge conversion as well as the reassembly of the micelle. Moreover, the disulfide linkages would be cleaved by GSH in the tumor cell cytoplasm, leading to rapid release of ibuprofen (Ibup) and further triggered CUR release. In vitro and in vivo anticancer studies on 4T1 cells and the anti-inflammatory experiment on RAW 264.7 cells demonstrated that this functional system possessed great dual-therapeutic ability. In addition, with the aid of the two-photon cell and deep tissue imaging of these AIE micelles, the in vitro and in vivo distribution of nanocarriers could be observed. Given the efficient dual therapy for tumor and inflammation and the two-photon cell and deep tissue imaging, these multi-functional micelles showed great potential for simultaneous cancer therapy, inflammation restraint and AIE active two-photon bioimaging.

Intelligent polymeric micelles with fluorescence imaging feature have been emerged as promising tools for theranostics. However, conventional fluorescent dyes are limited by short wavelength excitation, interference of tissue autofluorescence, limited imaging depth and quenched emission in aggregation state. Methods: We synthesized a novel mPEG-SS-Poly (AEMA-co-TBIS) (mPEATss) copolymer to develop multifunctional polymeric micelles with great AIE feature for cancer therapy and AIE active two-photon bioimaging. The stimuli-responsive behavior and AIE active two-photon cell and tissue imaging as well as in vitro and in vivo antitumor ability of DOX-loaded mPEATss were studied. Results: mPEATss micelles showed excellent AIE active two-photon cell imaging ability and deep tissue imaging ability. Antitumor drug DOX could be encapsulated to form a drug-loaded micellar system with a small diameter of 65 nm. The disassembly and charge-conversion of mPEATss micelles could be triggered by acidic environment, resulting in accelerated drug release and great antitumor efficacy. In vivo, ex vivo imaging and in vivo pharmacokinetic study demonstrated that mPEATss micelles could efficiently accumulate in tumor sites, which ensured ideal anticancer effect. Conclusions: This pH and redox dual responsive and AIE active two-photon imaging polymeric micelles would be a promising candidate for theranostics.

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.

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 β-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.

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.

In recent years, intelligent polymeric micelles with multifunctions are in urgent demand for cancer diagnosis and therapy. Herein, pH and redox dual-responsive prodrug micelles with aggregation-induced emission (AIE) active cellular imaging and charge conversion have been prepared for combined chemotherapy and bioimaging based on a novel doxorubicin-conjugated amphiphilic PMPC-PAEMA-P (TPE- co-HD)-ss-P (TPE- co-HD)-PAEMA-PMPC copolymer. The doxorubicin is conjugated via a pH cleavable imine linkage and can be packed in the hydrophobic core along with the glutathione (GSH)-sensitive disulfide bond. The DOX-conjugated inner core is sealed with a pH-responsive PAEMA as the "gate", which would rapidly open in the acidic condition, following the drug release and charge conversion-mediated acceleration of endocytosis. After an efficient internalization, the disulfide bond can be cleaved by the high concentration of GSH causing the further accelerated drug release. Meanwhile, intracellular drug delivery can be traced due to the AIE behavior of micelles. Moreover, great tumor inhibition in vitro and in vivo has been demonstrated for these DOX-conjugated micelles. This smart prodrug micelle system would be a desirable drug carrier for cancer therapy and bioimaging.

Valvular heart diseases lead to over 300,000 heart valve replacements worldwide each year. Bioprosthetic heart valves (BHVs), derived from glutaraldehyde (GLUT) crosslinked porcine or bovine pericardium, are often used. However, valve failure can occur within 12–15 years due to progressive degradation and/or calcification. Being innovated by previous amino reagent studies used for GLUT detoxification and carbodiimide [1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, EDC] chemistry, in this study, we developed a new fabrication method that utilizes exogenous amino donor arginine or lysine carbodiimide combined treatments to better stabilize the extracellular matrix of porcine pericardium. The carboxyl group density, amine content, differential scanning calorimetry, collagenase and elastase degradation, calcification by rat subdermal implantation, cytotoxicity, and platelet adhesion were characterized. We demonstrated that exogenous amino donor carbodiimide combined treatment for pericardiums had better resistance to elastase degradation (1.63 ± 0.11% and 1.44 ± 0.24% in arginine or lysine versus 3.68 ± 0.16% and 3.04 ± 0.11% in GLUT and GLUT/EDC control) and calcification (0.624 ± 0.193 and 0.637 ± 0.213 Ca µg/mg tissue in arginine or lysine versus 1.610 ± 0.124 and 1.512 ± 0.075 Ca µg/mg tissue in GLUT and GLUT/EDC control). This new strategy combined arginine or lysine and carbodiimide crosslinking would be a promising method to produce more robust BHVs with better structural stability and anticalcification property.

A strategy for construction of counterion-induced vesicles in aqueous media has been described using imidazolium salts with multiple imidazolium moieties and alkyl carboxylate counteranions. The spontaneous formation of vesicles can be achieved by the simple selection of the counteranion to satisfy the requirement of the packing parameter for vesicle formation. Functional fluorescent vesicles can also be formed by the introduction of an aggregation-induced emission (AIE) fluorophore, tetraphenylethene (TPE), as the core of the imidazolium salt TPEI-C8, which also exhibits highly specific nucleus imaging in living cells. Considering the distinct AIE characteristic of TPEI-C8, the aggregation-induced strong fluorescence emission of TPEI-C8 in the cell nucleus may be the main reason for the specific fluorescence images of the cell nucleus. The strategy for the construction of functional vesicles reported in this study has shown great potential for the construction of other functional vesicles.

Lipid droplets (LDs) have been regarded as potential targets for the diagnosis of cardiovascular diseases. However, conventional LDs imaging strategies suffer from invasive sample collection and tedious histological preparations. Although fluorescence imaging has showed good performance in LDs imaging, ideal probes are still in urgent demand. In this work, fluorescent probe, namely, MeTTI was prepared for LDs visualization in cells and tissues. MeTTI exhibited low fluorescence quantum yield in dimethyl sulfoxide (Φf = 0.2 %), while the value in the solid state was obvious increased (Φf = 3.5 %), suggesting the aggregation-induced emission (AIE) property of MeTTI. Meanwhile, MeTTI would form excimers (emission ranged 750–850 nm) in water, and it showed good biocompatibility. Moreover, MeTTI exhibited impressive fluorescence emission enhancement in oleic acid (Φf = 34.7 %) compared to that in water (Φf = 1.11 %), which can specifically stain LDs in cells, atherosclerosis (AS) plaques and human fibrocalcific bicuspid aortic valves (FBAV) with high ratio of signal to noise. In addition, MeTTI could also monitor the dynamic changes of LDs in cells. These results were expected to provide a simple tool for studying the pathogenesis of cardiovascular diseases with lipid deposition and triggering enthusiasm to develop new imaging techniques for the diagnosis of these diseases.

Intelligent nanocarriers for efficient drug delivery and bioimaging application are urgently demand. Herein, paclitaxel (PTX)-encapsulated redox-sensitive polymeric micelles based on tetraphenylethylene (TPE)-conjugated poly(D, L-lactide)-disulfide-poly(methacryloyloxyethyl phosphorylcholine) (TPE-PLA-SS-PMPC) copolymer has been developed for combined cancer therapy and aggregation induced emission (AIE) imaging. These biomimetic TPE-PLA-SS-PMPC micelles exhibit great biocompatibility and remarkable AIE features, showing great potential for bioimaging applications. PTX is loaded during the self-assembly process, and these drug-loaded micelles can disassemble quickly in the medium containing 10 mM glutathione to trigger rapid drug release and great growth inhibition of tumor cells. Moreover, these micelles can also be traced via fluorescent imaging of these AIE micelles. AIE active imaging and tumor cell growth inhibition, as well as excellent biocompatibility make these smart biomimetic micelles highly attractive as a prominent candidate for chemotherapy and bioimaging.

In the past few years, organic mechanochromic materials have attracted more and more attention and a number of organic mechanochromic materials have been reported. However, only a single mode for switching of mechanochromic luminescence, either red-shift or blue-shift of the luminescence, can be observed for all the reported mechanochromic materials. Herein, based on a single tributyl(perylen-3-ylmethyl)phosphonium (TPMP) fluorophore, dramatic dual-mode switchable mechanochromic luminescence triggered by tunable cation–anion interactions has been reported for the first time. The trend of mechanochromic luminescence changes gradually from a red-shift to a blue-shift along with the strength order of the cation–anion interaction: Br− > BF4− > PF6− > NTf2−. A reversible transition of a crystalline state to an amorphous phase might be involved in the mechanochromic luminescence of TPMP·X (X = counteranion) with different counteranions.

In recent years, fluorescent mitochondrial imaging has emerged as a powerful tool for monitoring the biological processes of mitochondria with high spatial and temporal resolution. However, conventional fluorescent reagents for mitochondrial imaging usually suffer from poor photostability and poor solubility in water as well as complex molecular structure and multi-step synthesis. Therefore, the development of an efficient method to construct specifically mitochondria-targeted molecules with superior photostability and aqueous solubility is in high demand for the study of mitochondrial functions. In this manuscript, a new type of aqueous-soluble fluorescent probe based on the perylene skeleton has been developed efficiently and exhibits high specificity to mitochondria with dual-emissive luminescence in living cells. To the best of our knowledge, this is the first report of a dual-emissive probe for specific mitochondrial imaging. Moreover, this perylene-based probe also exhibits superior photostability. The dual-emissive imaging, high specificity, and superior photostability as well as the efficient preparation make this perylene-based phosphonium fluorophore highly attractive as a fluorescent probe for mitochondrial imaging.

Organic mechanochromic fluorescent materials have attracted increasing interest over the last few years. However, organic mechanochromic fluorophores reported so far usually have complicated structures and require multi-step synthesis. In this paper, a simple method to design and synthesize organic mechanochromic fluorophores with simple structures and promising mechanochromic luminescence properties is reported. Based on this method, a broad range of pyrene-based phosphonium materials with promising mechanochromic luminescence have been developed. Among all pyrene-based mechanochromic materials reported so far, tributyl(pyren-1-ylmethyl)phosphonium fluorophore 1·PF6 reported in this paper is the smallest pyrene-based mechanochromic fluorophore with the longest emission wavelength shift. The method reported in this study has shown great potential for the rapid construction of mechanochromic materials and opened a new avenue to develop novel mechanochromic materials.

Intelligent polymeric micelles for antitumor drug delivery and tumor bioimaging have drawn a broad attention because of their reduced systemic toxicity, enhanced efficacy of drugs, and potential application of tumor diagnosis. Herein, we developed a multifunctional polymeric micelle system based on a pH and redox dual-responsive mPEG-P(TPE- co-AEMA) copolymer for stimuli-triggered drug release and aggregation-induced emission (AIE) active imaging. These mPEG-P(TPE- co-AEMA)-based micelles showed excellent biocompatibility and emission property, exhibiting great potential application for cellular imaging. Furthermore, the antitumor drug doxorubicin (DOX) could be encapsulated during self-assembly process with high loading efficiency, and a DOX-loaded micelle system with a size of 68.2 nm and narrow size distribution could be obtained. DOX-loaded micelles demonstrated great tumor suppression ability in vitro, and the dual-responsive triggered intracellular drug release could be further traced. Moreover, DOX-loaded micelles could efficiently accumulate at the tumor site because of enhanced permeability and retention effect and long circulation of micelles. Compared with free DOX, DOX-loaded micelles exhibited better antitumor effect and significantly reduced adverse effects. Given the efficient accumulation targeting to tumor tissue, dual-responsive drug release, and excellent AIE property, this polymeric micelle would be a potential candidate for cancer therapy and diagnosis.

A counterion-directed molecular design strategy is described for the spontaneous formation of stable vesicles via readily available imidazolium salts with the EDTA counterion in aqueous media. The counteranion is employed to adjust the balance between hydrophobic and hydrophilic parts, which satisfies the requirement of packing parameter for vesicle formation. The counterion-induced vesicles (CIVs) feature spontaneous formation, simple preparation, and easy availability of surfactants. Importantly, the unusual counterion-induced vesicle-like sphere aggregates can further chelate europium(III) ions to enhance the europium-centered emission in aqueous media and make it viable for an optical pH sensor, which exhibits a linear response in a wide range of pH values from 3 to 11. To the best of our knowledge, this constitutes one of the widest ranges of Eu-based pH sensors reported so far. This design concept has offered a new avenue for the preparation of functional vesicles.

Mechanofluorochromic materials have great potential for a wide variety of applications such as sensors, memory devices, motion systems, security systems, and so forth. However, only few design principles have been disclosed, which greatly impedes the growth of mechanofluorochromic dyes. Here, a strategy of molecular design for mechanochromic luminescence is reported, based on the cation–anion interaction-directed switching of molecular stacking. On the basis of this strategy, a series of common N-heteroaromatic onium fluorophores such as imidazolium, 1,2,4-triazolium, triazolopyridinium, benzoimidazolium, γ-carbolinium, and pyridinium salts have been designed and proved to have striking reversible mechanofluorochromic behaviors. The simple attachment of a non-fluorescent imidazolium unit to the pyrene scaffold through a flexible carbon chain can even trigger the mechanofluorochromic phenomenon, which gives a consummate interpretation that the cation–anion interaction can be considered as an important general tool to design organic mechanochromic luminescent materials.

The development of straightforward accesses to organic functional materials through C–H activation is a revolutionary trend in organic synthesis. In this article, we propose a concise strategy to construct a large library of donor–acceptor-type biheteroaryl fluorophores via the palladium-catalyzed oxidative C–H/C–H cross-coupling of electron-deficient 2H-indazoles with electron-rich heteroarenes. The directly coupled biheteroaryl fluorophores, named Indazo-Fluors, exhibit continuously tunable full-color emissions with quantum yields up to 93% and large Stokes shifts up to 8705 cm–1 in CH2Cl2. By further fine-tuning of the substituent on the core skeleton, Indazo-Fluor 3l (FW = 274; λem = 725 nm) is obtained as the lowest molecular weight near-infrared (NIR) fluorophore with emission wavelength over 720 nm in the solid state. The NIR dye 5h specifically lights up mitochondria in living cells with bright red luminescence. Typically, commercially available mitochondria trackers suffer from poor photostabilit...

The development of straightforward accesses to organic functional materials through C-H activation is a revolutionary trend in organic synthesis. In this article, we propose a concise strategy to construct a large library of donor-acceptor-type biheteroaryl fluorophores via the palladium-catalyzed oxidative C-H/C-H cross-coupling of electron-deficient 2H-indazoles with electron-rich heteroarenes. The directly coupled biheteroaryl fluorophores, named Indazo-Fluors, exhibit continuously tunable full-color emissions with quantum yields up to 93% and large Stokes shifts up to 8705 cm(-1) in CH2Cl2. By further fine-tuning of the substituent on the core skeleton, Indazo-Fluor 3l (FW = 274; λem = 725 nm) is obtained as the lowest molecular weight near-infrared (NIR) fluorophore with emission wavelength over 720 nm in the solid state. The NIR dye 5h specifically lights up mitochondria in living cells with bright red luminescence. Typically, commercially available mitochondria trackers suffer from poor photostability. Indazo-Fluor 5h exhibits superior photostability and very low cytotoxicity, which would be a prominent reagent for in vivo mitochondria imaging.

Relatively mild and highly efficient CuI-catalyzed N-arylation procedures for nitrogen-containing heterocycles (e.g., imidazoles, benzimidazoles, pyrroles, pyrazoles, indoles, triazoles, etc.) with aryl and heteroaryl halides have been developed. The protocols can be performed easily and tolerate a number of functional groups, such as ester, nitrile, nitro, ketone, free hydroxyl, and free primary amine on the aryl halide.

The selective catalytic oxidation of toluene with hydrogen peroxide over V-Mo-based catalysts under mild conditions was studied. The promotion effect of Mo on the catalysts was studied with V/Al2O3 and Mo/Al2O3 as reference samples. The catalysts were characterized by XRD, TPR, and XPS techniques. The results show that the addition of Mo to V/Al2O3 may change the distribution of V species on Al2O3 surface. Over V-Mo/Al2O3 catalyst, highly dispersed amorphous V species facilitates benzaldehyde formation, and crystalline V2O5 species increases the conversion of toluene but decreases the selectivity to benzaldehyde, while AlVMoO7 species favors both the conversion of toluene and the formation of cresols. The yield of benzaldehyde depends remarkably on the surface O/Al and Mo/V atomic ratios, and gets to a maximum value of 13.2% with a selectivity of 79.5% at an O/Al atomic ratio of 3.0 and Mo/V atomic ratio of 0.7.

Smart nanocarrier for simultaneous drug delivery and cellular imaging is ideal for both cancer therapy and diagnosis. In this work, polymeric micelles based on the tetraphenylethene (TPE) conjugated poly(N6-carbobenzyloxy-l-lysine)-block-poly(2-methacryloyloxyethyl phosphorylcholine) (TPE-PLys-b-PMPC) copolymer are successfully prepared. Such biomimetic and biodegradable TPE-PLys-b-PMPC micelles exhibit remarkable aggregation-induced emission (AIE) feature and great biocompatibility, showing great potential for bioimaging application. In addition, anticancer drug doxorubicin (DOX) can be incorporated into the core of micelles and the intracellular release of DOX can be furthermore traced through the fluorescent imaging of these AIE micelles. As expected, this DOX-loading polymeric micelle shows significant growth inhibition against HeLa cells and 4T1 cells and such TPE-PLys-b-PMPC micelles would be a promising drug carrier for potential cancer therapy and bioimaging. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45651.

Rhodium-catalyzed carbon-hydrogen bond activation has attracted great interest in the construction of carbon-carbon and carbon-heteroatom bonds. In recent years, transition metal-mediated oxygen transposition through a 'dehydration-rehydration' process has been considered as a promising strategy towards oxygen-functionalized compounds. Here we describe an unexpected rhodium-catalyzed regioselective carbon-hydrogen bond activation/cyclization of easily available indolyl aldehydes or ketones with alkynes to afford benzo-fused oxindoles, involving the sequential carbonyl-assisted carbon-hydrogen activation of the indole ring at the 4-position, [4+2] cyclization, aromatization via dehydration, nucleophilic addition of water to iminium and oxidation. Isotopic labelling experiments disclose the occurrence of apparent oxygen transposition via dehydration-rehydration from the indolyl-3-carbonyl group to the 2-position of pyrrole to forge a new carbonyl bond. The tandem reaction has been used as the key step for the concise synthesis of priolines, a type of alkaloid isolated from the roots of Salvia prionitis.

A copper-catalyzed process has been developed for the N-arylation reaction under very mild conditions in the absence of additional ligand. This protocol could not only tolerate an array of thermally sensitive functional groups, but also achieve high chemoselectivity.