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We disclose a visible-light-promoted aerobic alkylation of activated C(sp3)–H bonds using pyrenedione (PYD) as the photocatalyst. Direct C–H bond alkylation of tetrahydrofuran with alkylidenemalononitriles is accomplished in over 90% yield in the presence of 5 mol% of PYD and 18 W blue LED light under ambient conditions. The substrate scope is extended to ethers, thioethers, and allylic C–H bonds in reactions with various electrophilic Michael acceptors. The catalytic turnover process is facilitated by oxygen. Our work represents the first example of using PYD as a photocatalyst to promote C(sp3)–H alkylation, revealing the unique character of PYD as a novel organophotocatalyst.

Pyrenediones (PYDs) are efficient photocatalysts for three oxygenation reactions: epoxidation of electron deficient olefins, oxidative hydroxylation of organoborons, and oxidation of sulfides via in situ generation of H2O2 under visible light irradiation, using oxygen as a terminal oxidant and IPA as a solvent and a hydrogen donor.

Recently, a great effort has been made to perfect the therapeutic effect of solid tumor, from single-agent therapy to combined therapy and many other polymer-drug conjugations with dual or more anticancer agents due to their promising synergistic effect and higher drug level accumulation towards tumor tissues. Different polymer-drug spacers present diverse therapeutic efficacy, therefore, finding an appropriate spacer is desirable. In this study, dual drugs that are doxorubicin (DOX) and mitomycin C (MMC) were conjugated onto a polymer carrier (xyloglucan) via various peptide or amide bonds, and a series of polymers drug conjugates were synthesized with different spacers and their effect on tumor treatment efficacy was studied both in vitro and in vivo. The result shows that the synergistic effect is better when using different linker to conjugate different drugs rather than using the same spacer to conjugate different drugs on the carrier. Particularly, the finding of this works suggested that, using peptide bond for MMC and amide bond for DOX to conjugate dual drugs onto single XG carrier could improve therapeutic effect and synergy effect. Therefore, in polymer-pharmaceutical formulations, the use of different spacers to optimize the design of existing drugs to enhance therapeutic effects is a promising strategy.

Herein, we report on fluorophore-tagged Grubbs catalysts as turn-on fluorescent probes for the sensitive detection and quantitation of ethylene, a plant hormone that plays a critical role in many phases of plant growth and fruit ripening. The ruthenium-based weak fluorescent probes were prepared handily through the metathesis reaction between the first-generation Grubbs catalyst and selected fluorophores that have high quantum yields and contain terminal vinyl groups. Upon exposure to ethylene, fluorescence enhancement was observed via the release of fluorophore from the probe. Our probe shows an excellent limit of detection for ethylene at 0.9 ppm in air and was successfully applied for monitoring ethylene released during the fruit-ripening process. Our work opens up a new avenue of application of Grubbs catalysts for bioanalytical chemistry of ethylene, which is critically important in plant biology, agriculture, and food industry.

Singlet oxygen plays an important role in cancer chemotherapy and biology of reactive oxygen species. In recent years, there are some reports of selective fluorescent probes for detection and imaging of singlet oxygen but the existing probes have some major drawbacks including complicated synthetic routes, poor fluorescence enhancement effects. We report herein that anthracenylmethyl modified non-fluorescent derivatives of fluorescein and rhodamine-6G can reacts with 1O2, which resulted in C C bond cleavage that detach anthracene unit from the fluorophores resulting in strong fluorescence enhancement. These probes exhibit high selectivity and sensitivity in detection and imaging of 1O2 in chemical and in living cells. Our approach makes it simple and flexible for development of reaction-based 1O2 fluorescent probes for broad application in chemical, biomedical, and environmental sciences.

The synthesis, characterization, and application of a near infrared (NIR) fluorescent singlet oxygen (1O2) probe was reported. The probe employs an IR-780 as the fluorophore, and a dimethylhomoocoerdianthrone (HOCD) moiety as the fluorescence quencher as well as the reaction center for 1O2. At its original state, the fluorescence is quenched due to photo-induced electron transfer, while when reacted with 1O2, the quenching is abolished, and fluorescence turns on for nearly 30 folds. The probe showed good selectivity and sensitivity towards 1O2 and was able to Image 1O2 in vivo in simulated photo dynamic therapy in mice carcass. Besides, a fluorescent method for quantifying 1O2 quenching capacity was established and was applied to measure the 1O2 quenching of flavonoids. The 1O2 scavenging activity is dependent on the structures of the flavonoids and morin is the most active singlet oxygen scavenger among the flavonoids measured and the rest of the compounds show only moderate activity.

We report a sensitive and selective method for detection and quantification of tryptophan and cysteine utilizing 1,8-pyrenedione as turn-on fluorescent probe. Non-fluorescent PYRENEDIONE was hydrogenated to highly fluorescent 1,8-pyrenediol by tryptophan and cysteine, but not by other amino acids, within minutes at room temperature. Dose dependent fluorescent turn-on were observed for both cysteine and tryptophan (linear range: 0–7 μM, R2 = 0.9930; LOD 0.15 μM; LOQ 0.45 μM). The method shows good accuracy with spike and recovery rate of 92.1–106.4% and excellent precision with run-to-run variation of smaller than 4.0%. The validated assay was successfully applied to quantify tryptophan contents in soy sauce. Our results shown that the content of tryptophan in naturally fermented soy sauce ranges from 34 to 891 μM while it is low (

We discovered a reaction between 1,8-pyrenedione and N,N′-dialkylethylenediamine to form highly fluorescent products, via aza-Michael addition followed by double C–H activation facilitated by visible light. Remarkably, the reaction intermediates and mono C–H bond activation product could only be formed when the reaction was carried out in the presence of a base and UV-light (254 nm). Dehydrogenation of the intermediate under room lighting converts it to the final products. The reaction is a general one as it works with a number of ethyleneamines with different substituents with a (N)–CHn (n = 1, 2) linkage. The reaction mechanisms suggested that nucleophilic addition of the amine followed by dehydrogenation occurs to restore aromaticity and give an amine substituted 1,8-pyrenedione intermediate. The C–H activation requires photoexcitation via a radical mechanism. Our work opens a new avenue for the construction of novel molecules with a pyrene core as a fluorophore with good quantum yields.

Hepatocellular carcinoma (HCC) is still considered as the third highest cause of cancer death in developing countries. In our previous study, we confirmed that the galactose residues of natural polysaccharide xyloglucan (XG) turns out to be selected uptake by asialoglycoprotein receptor (ASGPR) and the xyloglucan can be used as drug carriers and achieve some enhancement in the therapeutic effect of HCC via ASGPR mediated endocytosis. In this study, we selected mitomycin C (MMC) as the anticancer model drug and a macromolecular drug delivery system (DDS) with different degrees of substitution that was synthesized by conjugating mitomycin C with xyloglucan. The degree of substitution of xyloglucan–mitomycin C conjugates (XG–MMC) was about 9.7%. Another sample obtained a higher degree of substitution (p-MMC) of approximately 31%. The content of MMC in XG–MMC and p-MMC was determined and calculated to be about 3.1% and 6.4%, respectively. In the in vitro cytotoxicity experiment, the prodrugs presented higher cytotoxicity than free MMC against the drug resistant HepG2 cells. Moreover, the IC50 of XG–MMC (0.997 μg mL−1) was much lower than that of p-MMC (2.56 μg mL−1) and XG–MMC exhibited higher drug uptake amounts (187.9 ng) than that of p-MMC (63.5 ng). The in vivo cytotoxicity was also evaluated, and the result was in good agreement with the in vitro cytotoxicity experiment.

An active-targeting and smart pH-sensitive nanoparticle drug delivery system with high drug loading was developed by conjugating doxorubicin (DOX) to xyloglucan (XG) through acid-cleavable hydrazone bonds, and then encapsulating DOX by the self-assembly of xyloglucan–doxorubicin conjugates (XG–DOX) to ensure a sufficient amount of drug delivered in the tumor region. The galactose moiety of XG, as an ideal targeting moiety, could be recognized and internalized by asialoglycoprotein receptor (ASGP-R), which is especially ample in hepatocytes. And then the abundant DOX of xyloglucan–doxorubicin nanoparticle drug delivery systems (DOX nano-DDSs) could be highly accumulated and released in drug resistant tumor cells to exert maximum therapeutic effects. Compared with free DOX, the novel DOX nano-DDSs apparently showed longer circulation time, larger intracellular uptake, more drug release, higher cytotoxicity against drug resistant HepG2 (HepG2/DOX) cells and greater effects for inhibiting the growth of the tumor volume and decreasing systemic toxicity. Even though there was no significant enhancement in intracellular uptake and cytotoxicity between the DOX nano-DDSs and XG–DOX, the loading content of DOX of DOX nano-DDSs reached 23%, which is higher than that of XG–DOX conjugates. Moreover, the DOX nano-DDSs obviously presented better anti-tumor effects in in vivo assays. In conclusion, these novel DOX nano-DDSs exhibited remarkable anti-tumor effects and few side effects, which is significantly promising for the clinical therapy of cancer.

A major challenge of combinatorial therapy is the unification of the pharmacokinetics and cellular uptake of various drug molecules with precise control of the dosage thereby maximizing the combined effects. To realize ratiometric delivery and synchronized release of different drugs from a single carrier, a novel approach was designed in this study to load dual drugs onto the macromolecular carrier with different molar ratio by covalently preconjugating dual drugs through peptide linkers to form drug conjugates. In contrast to loading individual types of drugs separately, these drug conjugates enable the loading of dual drugs onto the same carrier in a precisely controllable manner to reverse multidrug resistance (MDR) of human hepatoma (HepG2) cells. As a proof of concept, the synthesis and characterization of xyloglucan-mitomycin C/doxorubicin (XG-MMC/DOX) conjugates were demonstrated. This approach enabled MMC and DOX to be conjugated to the same polymeric carrier with precise control of drug dosage. The cytotoxicity and combinatorial effects were significantly improved compared to the cocktail mixtures of XG-MMC and XG-DOX as well as the individual conjugate of the mixture. Moreover, the results also showed that there was an optimum ratio of dual drugs showing the best cytotoxicity effect and greatest synergy among other tested polymeric conjugate formulations.

A folate-targeted dextran–doxorubicin conjugate (folate–dextran–DOX) for drug delivery systems (DDSs) was synthesized by grafting DOX onto dextran through cleavable hydrazone bonds and a pH-sensitive spacer for controlling the drug release. Folate was coupled onto dextran as an ideal ligand for targeting hepatocytes. The conjugate was formulated into nanoparticles with excessive deprotonated DOX (DOX nano-DDSs) under aqueous conditions, which exhibited nanoparticles with larger size of 147.9 nm in diameter and improved drug entrapment to the level of 25.2%. DOX nano-DDSs delivered higher cytotoxicity and a greater extent of intracellular uptake in vitro against drug resistant HepG2 (HepG2/DOX) cells; moreover, they displayed equivalent effects with folate–dextran–DOX micelles in terms of inhibiting tumor volume and decreasing toxicity. In addition, DOX nano-DDSs achieved significantly greater effects than free DOX. The results indicated that these targeted self-organized DOX nano-DDSs have superior reversal efficacy to free DOX and serve as a highly promising nano-platform for future cancer therapy.

Therapy is complex since several drugs need to be with coordinated with different routes, while considered their side effects and mechanisms of resistance. A combination of various undesirable factors, including biological surroundings, poor solubility, and instability of many potential drugs within biological systems and systemic toxicity of drugs have necessitated nanoparticles to optimize drug delivery. Although, in theory, combined therapy could provide a promising strategy over single-agent therapy, appreciable therapeutic efficiency is not generally found, whereas multidrug toxicity is frequently found in clinical situations. Nanoparticles for drug combinations can elicit synergisms among them, enhance the physical stability, and decrease the side effects of drugs as they can achieve unification of the pharmacokinetics and cellular uptake of various drug molecules. These carriers can improve their selective accumulation for the tumor by passive and/or active targeting mechanisms. In general, combination therapy with nanosized drug delivery systems will hopefully result in increased patient compliance and better outcomes.

10-Hydroxycamptothecin (HCPT) is a clinical therapy agent against hepatoma. The chemotherapy of HCPT is strongly obstructed by the emergence of multidrug resistance (MDR), serious systemic toxicity, malfunction of rapid phagocytic and renal clearance disorder which are undesirable for its chemotherapy. In this paper, a drug delivery system (DDS) for HCPT has been developed in order to overcome MDR. Nanostructured lipid carriers (NLC) coated with xyloglucan (XG) was prepared by soya oil and XG consisting of side chains with galactose residues, a terminal moiety that can be used to target HCPT to hepatoma. The therapeutic potential of XG-NLC/HCPT was investigated on HepG2/HCPT cells and on human tumor xenograft nude mouse model (implanted with HepG2/HCPT cells). XG-NLC/HCPT not only indicated superior cytotoxicity against the drug resistant HepG2 cells but also in vivo, generated a higher therapeutic effect. Systemic toxicity study demonstrated that the carrier reduced systemic toxicity. XG-NLC/HCPT proved a great potential to serve as DDS to overcome MDR of HepG2/HCPT cells. These results suggested that XG NLC/HCPT represent a promising carrier for drug delivery to the hepatoma and reverse the drug resistant of HepG2 cells and XG could be exploited as a potential targeting device for liver tissue.