A portable smartphone platform utilizing dual-sensing signals for visual determination of semicarbazide in food samples.

Semicarbazide (SEM) is a metabolite of antibiotic nitrofurazone and a food contaminant in food production, showing potential carcinogenic, mutagenic, teratogenic, and toxic effects on human health. It is urgent to develop a highly efficient and sensitive assay for visual detection of SEM. In this paper, a pyrrolopyrrole cyanine fluorescent probe (PPCy-1) was reported for visualization and quantitative analysis of SEM through a chromophore reaction sensing mechanism for the first time. The probe towards SEM exhibited a fast response (10 min), a low detection limit (0.18 µM), high selectivity, and distinct dual ratiometric fluorescence turn-on and colorimetric modes. Its practicability was further verified by detecting SEM in meat, water, and honey samples with satisfactory recovery values. More importantly, a smartphone-assisted portable testing platform was constructed based on a PPCy-1-immobilized test paper or a polyamide thin film with a color scanning APP for real-time and on-site detection of SEM. This work provides low-cost, convenient, and rapid assays for visual SEM detection, which have potential applications in food safety monitoring.

Combination of disulfiram and Copper-Cysteamine nanoparticles induces mitochondria damage and promotes apoptosis in endometrial cancer.

Endometrial cancer (EC) stands as one of the most prevalent gynecological malignancies affecting women, with its incidence and disease-related mortality steadily on the rise. Disulfiram (DSF), an FDA-approved medication primarily used for treating alcohol addiction, has exhibited promising anti-tumor properties. Studies have revealed DSF's capacity for enhanced anti-tumor activity, particularly when combined with copper. The novel Copper-Cysteamine (CuCy) compound, Cu3Cl(SR)2 (R[bond, double bond]CH2CH2NH2), showcases photodynamic effects and demonstrates significant anti-tumor potential under various conditions, including exposure to ultraviolet light, X-ray, microwave, and ultrasound. This study delves into exploring the synergistic anti-tumor effects and underlying mechanisms by utilizing copper-cysteamine in conjunction with DSF against endometrial cancer. The investigation involved comprehensive analyses encompassing in vitro experiments utilizing Ishikawa cells, in vivo studies, and transcriptomic analyses. Remarkably, the combined administration of both compounds at a low dose of 0.5 µM exhibited pronounced efficacy in impeding tumor growth, inhibiting blood vessel formation, and stimulating cell apoptosis. Notably, experiments involving transplanted tumors in nude mice vividly demonstrated the significant in vivo anti-tumor effects of this combination treatment. Detailed examination through transmission electron microscopy unveiled compelling evidence of mitochondrial damage, cellular swelling, and rupture, indicative of apoptotic changes in morphology due to the combined treatment. Moreover, transcriptomic analysis unveiled substantial downregulation of mitochondrial-related genes at the molecular level, coupled with a significant hindrance in the DNA repair pathway. These findings strongly suggest that the combined application of CuCy and DSF induces mitochondrial impairment in Ishikawa cells, thereby fostering apoptosis and ultimately yielding potent anti-tumor effects.

Sorafenib-Based Drug Delivery Systems: Applications and Perspectives.

As a Food and Drug Administration (FDA)-approved molecular-targeted chemotherapeutic drug, sorafenib (SF) can inhibit angiogenesis and tumor cell proliferation, leading to improved patient overall survival of hepatocellular carcinoma (HCC). In addition, SF is an oral multikinase inhibitor as a single-agent therapy in renal cell carcinoma. However, the poor aqueous solubility, low bioavailability, unfavorable pharmacokinetic properties and undesirable side effects (anorexia, gastrointestinal bleeding, and severe skin toxicity, etc.) seriously limit its clinical application. To overcome these drawbacks, the entrapment of SF into nanocarriers by nanoformulations is an effective strategy, which delivers SF in a target tumor with decreased adverse effects and improved treatment efficacy. In this review, significant advances and design strategies of SF nanodelivery systems from 2012 to 2023 are summarized. The review is organized by type of carriers including natural biomacromolecule (lipid, chitosan, cyclodextrin, etc.); synthetic polymer (poly(lactic-co-glycolic acid), polyethyleneimine, brush copolymer, etc.); mesoporous silica; gold nanoparticles; and others. Co-delivery of SF and other active agents (glypican-3, hyaluronic acid, apolipoprotein peptide, folate, and superparamagnetic iron oxide nanoparticles) for targeted SF nanosystems and synergistic drug combinations are also highlighted. All these studies showed promising results for targeted treatment of HCC and other cancers by SF-based nanomedicines. The outlook, challenges and future opportunities for the development of SF-based drug delivery are presented.

Recent advances in type I organic photosensitizers for efficient photodynamic therapy for overcoming tumor hypoxia.

Photodynamic therapy (PDT) with an oxygen-dependent character is a noninvasive therapeutic method for cancer treatment. However, its clinical therapeutic effect is greatly restricted by tumor hypoxia. What's more, both PDT-mediated oxygen consumption and microvascular damage aggravate tumor hypoxia, thus, further impeding therapeutic outcomes. Compared to type II PDT with high oxygen dependence and high oxygen consumption, type I PDT with less oxygen consumption exhibits great potential to overcome the vicious hypoxic plight in solid tumors. Type I photosensitizers (PSs) are significantly important for determining the therapeutic efficacy of PDT, which performs an electron transfer photochemical reaction with the surrounding oxygen/substrates to generate highly cytotoxic free radicals such as superoxide radicals (˙O2-) as type I ROS. In particular, the primary precursor (˙O2-) would progressively undergo a superoxide dismutase (SOD)-mediated disproportionation reaction and a Haber-Weiss/Fenton reaction, yielding higher cytotoxic species (˙OH) with better anticancer effects. As a result, developing high-performance type I PSs to treat hypoxic tumors has become more and more important and urgent. Herein, the latest progress of organic type I PSs (such as AIE-active cationic/neutral PSs, cationic/neutral PSs, polymer-based PSs and supramolecular self-assembled PSs) for monotherapy or synergistic therapeutic modalities is summarized. The molecular design principles and strategies (donor-acceptor system, anion-π+ incorporation, polymerization and cationization) are highlighted. Furthermore, the future challenges and prospects of type I PSs in hypoxia-overcoming PDT are proposed.

Recent Advances of Diketopyrrolopyrrole Derivatives in Cancer Therapy and Imaging Applications.

Cancer is threatening the survival of human beings all over the world. Phototherapy (including photothermal therapy (PTT) and photodynamic therapy (PDT)) and bioimaging are important tools for imaging-mediated cancer theranostics. Diketopyrrolopyrrole (DPP) dyes have received more attention due to their high thermal and photochemical stability, efficient reactive oxygen species (ROS) generation and thermal effects, easy functionalization, and tunable photophysical properties. In this review, we outline the latest achievements of DPP derivatives in cancer therapy and imaging over the past three years. DPP-based conjugated polymers and small molecules for detection, bioimaging, PTT, photoacoustic imaging (PAI)-guided PTT, and PDT/PTT combination therapy are summarized. Their design principles and chemical structures are highlighted. The outlook, challenges, and future opportunities for the development of DPP derivatives are also presented, which will give a future perspective for cancer treatment.

Recent Advances in Fluorescent Methods for Polyamine Detection and the Polyamine Suppressing Strategy in Tumor Treatment.

The biogenic aliphatic polyamines (spermine, spermidine, and putrescine) are responsible for numerous cell functions, including cell proliferation, the stabilization of nucleic acid conformations, cell division, homeostasis, gene expression, and protein synthesis in living organisms. The change of polyamine concentrations in the urine or blood is usually related to the presence of malignant tumors and is regarded as a biomarker for the early diagnosis of cancer. Therefore, the detection of polyamine levels in physiological fluids can provide valuable information in terms of cancer diagnosis and in monitoring therapeutic effects. In this review, we summarize the recent advances in fluorescent methods for polyamine detection (supramolecular fluorescent sensing systems, fluorescent probes based on the chromophore reaction, fluorescent small molecules, and fluorescent nanoparticles). In addition, tumor polyamine-suppressing strategies (such as polyamine conjugate, polyamine analogs, combinations that target multiple components, spermine-responsive supramolecular chemotherapy, a combination of polyamine consumption and photodynamic therapy, etc.) are highlighted. We hope that this review promotes the development of more efficient polyamine detection methods and provides a comprehensive understanding of polyamine-based tumor suppressor strategies.

Characterization of nanoparticles combining polyamine detection with photodynamic therapy.

Polyamine detection and depletion have been extensively investigated for cancer prevention and treatment. However, the therapeutic efficacy is far from satisfactory, mainly due to a polyamine compensation mechanism from the systemic circulation in the tumor environment. Herein, we explore a new solution for improving polyamine detection as well as a possible consumption therapy based on a new photosensitizer that can efficiently consume polyamines via an irreversible chemical reaction. The new photosensitizer is pyrrolopyrroleaza-BODIPY pyridinium salt (PPAB-PyS) nanoparticles that can react with the over-expressed polyamine in cancer cells and produce two photosensitizers with enhanced phototoxicity on cancer destruction. Meanwhile, PPAB-PyS nanoparticles provide a simultaneous ratiometric fluorescence imaging of intracellular polyamine. This combination polyamine consumption with a chemical reaction provides a new modality to enable polyamine detection along with photodynamic therapy as well as a putative depletion of polyamines for cancer treatment and prevention.

Pyridinium-substituted tetraphenylethylene salt-based photosensitizers by varying counter anions: a highly efficient photodynamic therapy for cancer cell ablation and bacterial inactivation.

Cancer and bacterial infection seriously threaten the health of human beings. The development of an image-guided photosensitizer with a "Two-in-One" function that can be simultaneously used for both efficient cancer cell ablation and rapid bacterial inactivation is highly in demand. In this project, we designed and prepared two aggregation-induced emission luminogens (AIEgens) (called TPEPy-I and TPEPy-PF6) with a strong electron push-pull effect. They have a near-infrared (NIR) emission, a high 1O2 quantum yield up to 0.93 and a fluorescence turn-on effect in mitochondria. Upon white light irradiation, the two mitochondria-targeting AIEgens exhibit a highly efficient photodynamic ablation of HeLa cells as well as excellent photodynamic inactivation of both Gram-positive S. aureus and Gram-negative E. coli. The time-dependent density functional theory (TD-DFT) results indicate that compared to TPEPy-PF6, TPEPy-I can easily produce the triplet state that is a prerequisite for 1O2 formation. Moreover, the positive effect of iodide anions gives TPEPy-I a higher photodynamic efficacy in cancer cell ablation and bacterial inactivation as compared with TPEPy-PF6.

Pillar[5]arene-Diketopyrrolopyrrole Fluorescent Copolymer: A Promising Recognition and Adsorption Material for Adiponitrile by Selective Formation of a Conjugated Polypseudorotaxane.

Conjugated pillar[5]arene-diketopyrrolopyrrole copolymer (P1) is synthesized by the copolymerization of a difunctionalized pillar[5]arene and a diketopyrrolopyrrole-based monomer, which shows large extinction coefficients (1.1 × 104 m-1 cm-1 ) at 519 nm and strong emission at 587 nm. P1 exhibits very strong host-guest binding affinity towards adiponitrile but low binding affinity towards 1,4-dihalobutane and 1,4-bis(imidazol-1-yl)butane. Such an enhanced selectivity is first found in the polypseudorotaxane between pillararene and neutral guests in organic solution and is successfully used for the recognition and adsorption of adiponitrile by the formation of a P1-adiponitrile polypseudorotaxane.

Amphiphilic xanthones as a potent chemical entity of anti-mycobacterial agents with membrane-targeting properties.

Tuberculosis (TB) remains a deadly disease and infects one-third of the world's population. Given the low success rates encountered in clinical development, there is an urgent need to identify structurally novel antimicrobials for tuberculosis. The present report details the anti-mycobacterial activities, structure-activity relationships (SARs) and mechanism of action of amphiphilic xanthone derivatives. The xanthones exhibited potent MIC, rapid time-kill and no cross-resistance with the current anti-TB drugs. Evidence is presented that these compounds disrupted the inner membrane and led to ATP depletion. Amphiphilic xanthone derivatives exhibited superior metabolic stability, low cytotoxicity and low activity against the common cytochrome P450. Compound 5 was selected for an in vivo pharmacokinetic study. Its bioavailability at an oral dose of 2 mg/kg was 15%. The xanthones thuse provide valuable insight for the development of a new class of membrane targeting antimycobacterial agents that may assist in overcoming the limitations of the current TB medications.

Nonpeptidic Amphiphilic Xanthone Derivatives: Structure-Activity Relationship and Membrane-Targeting Properties.

We recently reported the bioinspired synthesis of a highly potent nonpeptidic xanthone, 2c (AM-0016), with potent antibacterial activity against MRSA. Herein, we report a thorough structure-activity relationship (SAR) analysis of a series of nonpeptidic amphiphilic xanthone derivatives in an attempt to identify more potent compounds with lower hemolytic activity and greater membrane selectivity. Forty-six amphiphilic xanthone derivatives were analyzed in this study and structurally classified into four groups based on spacer length, cationic moieties, lipophilic chains, and triarm functionalization. We evaluated and explored the effects of the structures on their membrane-targeting properties. The SAR analysis successfully identified 3a with potent MICs (1.56-3.125 µ/mL) and lower hemolytic activity (80.2 µg/mL for 3a versus 19.7 µg/mL for 2c). Compound 3a displayed a membrane selectivity of 25.7-50.4. Thus, 3a with improved HC50 value and promising selectivity could be used as a lead compound for further structural optimization for the treatment of MRSA infection.

A highly selective and sensitive photoswitchable fluorescent probe for Hg2+ based on bisthienylethene-rhodamine 6G dyad and for live cells imaging.

A new photochromic diarylethene derivative bearing rhodamine 6G dimmer as a fluorescent molecular probe is designed and synthesized successfully. All the compounds are characterized by nuclear magnetic resonance and mass spectrometry. The bisthienylethene-rhodamine 6G dyad exhibit excellent phtochromism with reversibly color and fluorescence changes alternating irradiation with ultraviolet and visible light. Upon addition of Hg(2+), its color changes from colorless to red and its fluorescence is remarkably enhanced. Whereas other ions including K(+), Na(+), Ca(2+), Mg(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Mn(2+), Pb(2+), Ni(2+), Fe(3+), Al(3+), Cr(3+) and so on induce basically no spectral changes, which constitute a highly selective and sensitive photoswitchable fluorescent probe toward Hg(2+). Furthermore, by means of laser confocal scanning microscopy experiments, it is demonstrated that this probe can be applied for live cell imaging and monitoring Hg(2+) in living lung cancer cells with satisfying results, which shows its value of potential application in environmental and biological systems.

Iron-catalyzed domino process for the synthesis of alpha-carbonyl furan derivatives via one-pot cyclization reaction.

The Fe(ClO(4))(3)-catalyzed intramolecular rearrangement/cyclization/oxidation reaction sequence for the synthesis of alpha-carbonyl furan derivatives from electron-deficient alkynes and 2-yn-1-ols is reported.

A dendrimer chiroptical switch based on the reversible intramolecular photoreaction of anthracene and benzene rings.

A series of Fréchet-type dendrimers with 9-benzyloxymethylanthracene cores were synthesized and characterized. The chiral source for the dendrimers was an (S)-2-methyl-1-butoxy group in the 3-position of the benzene ring. Irradiation at 366 nm of a dilute benzene solution led to the formation of two diastereomers (1:1) through a quantitative intramolecular [4pi+4pi] cycloaddition between the central anthracene ring and the neighboring benzene ring. The process can be reversed with 254 nm UV light or heat. The benzene rings in the dendrons work as a light-harvesting system. The optical rotation values measured for the reversible process showed fatigue resistance. Thus, a promising new type of chiroptical switch has been created that has optical rotation values as output signals.

Synthesis and potent antileukemic activities of 10-benzyl-9(10H)-acridinones.

A novel series of 10-benzyl-9(10H)-acridinones and 1-benzyl-4-piperidones were synthesized and tested for their in vitro antitumor activities against CCRF-CEM cells. Assay-based antiproliferative activity study using CCRF-CEM cell lines revealed that the acridone group and the substitution pattern on the benzene unit had significant effect on cytotoxicity of this series of compounds, among which 10-(3,5-dimethoxy)benzyl-9(10H)-acridinone (3b) was found to be the most active compound with IC(50) at about 0.7 microM. Compound 3b was also found to have antiproliferative activity against two other human leukemic cell lines K562 and HL60 using the MTT assay. The antitumor effect of 3b is believed to be due to the induction of apoptosis, which is further confirmed by PI (Propidium iodide) staining and Annexin V-FITC/PI staining assay using flow cytometry analysis.

Total synthesis of epothilone a through stereospecific epoxidation of the p-methoxybenzyl ether of epothilone C.

The total synthesis of epothilone A is described by the coupling four segments 4-7 a. Three of the segments, 4, 5 and 7 a, have only one chiral center; all other chiral centers were introduced by simple asymmetric catalytic reactions. The key steps are the ring opening of epoxide 5 with acetylide 8 for the construction of the C12-C13 cis double bond and a practical hydrolytic kinetic resolution (HKR) developed by Jacobsen group for the introduction the chiral center at C3. Especially, the stereospecific epoxidation of 3-O-PMB epothilone C 3 b through long-range effect of 3-O-PMB protecting group gave high yields of the C12-C13 alpha-epoxide for the synthesis of target molecule.