A novel NIR fluorescent probe inhibits melanoma progression through apoptosis and ERK/DRP1-mediated mitochondrial fission.

Melanoma, a highly metastatic malignant tumour, necessitated early detection and intervention. This study focuses on a hemicyanine fluorescent probe activated by near-infrared (NIR) light for bioimaging and targeted mitochondrial action in melanoma cells. IR-418, our newly designed hemicyanine-based NIR fluorescent probe, demonstrated effective targeting of melanoma cell mitochondria for NIR imaging.

Multifunctional Near-Infrared Dye IR-817 Encapsulated in Albumin Nanoparticles for Enhanced Imaging and Photothermal Therapy in Melanoma.

Background: Near-infrared cyanine dyes have high sensitivity and spatial resolution imaging capabilities, but they also have unavoidable drawbacks such as photobleaching, low water solubility, fluorescence quenching, and toxic side effects. As an effective biologic drug carrier, albumin combines with cyanine dyes to form albumin@dye nanoparticles. These nanoparticles can alleviate the aforementioned issues and are widely used in tumor imaging and photothermal therapy.

A novel mitochondria-targeting compound exerts therapeutic effects against melanoma by inducing mitochondria-mediated apoptosis and autophagy in vitro and in vivo.

Melanoma is the most invasive skin cancer, with a high mortality rate. However, existing therapeutic drugs have side effects, low reactivity, and lead to drug resistance. As the power source in cells, mitochondria play an important role in the survival of cancer cells and are an important target for tumor therapy.

A novel multifunctional mitochondrion-targeting NIR fluorophore probe inhibits tumour proliferation and metastasis through the PPARγ/ROS/β-catenin pathway.

Recent advancements in tumour-targeted therapies and immunotherapy offer hope to patients with various malignancies. However, the uncontrolled growth and metastatic infiltration of malignant tumours remain a huge therapeutic challenge. Therefore, this study aimed to develop an integrated multifunctional diagnostic and treatment reagent IR-251 that can not only be used for tumour imaging but also to inhibit tumour growth and metastasis.

The SARS-CoV-2 nucleocapsid protein: its role in the viral life cycle, structure and functions, and use as a potential target in the development of vaccines and diagnostics.

Coronavirus disease 2019 (COVID-19) continues to take a heavy toll on personal health, healthcare systems, and economies around the globe. Scientists are expending tremendous effort to develop diagnostic technologies for detecting positive infections within the shortest possible time, and vaccines and drugs specifically for the prevention and treatment of COVID-19 disease. At the same time, emerging novel variants have raised serious concerns about vaccine efficacy.

Mitochondrion-Targeted NIR Therapeutic Agent Suppresses Melanoma by Inducing Apoptosis and Cell Cycle Arrest via E2F/Cyclin/CDK Pathway.

Malignant melanoma is the most fatal form of skin cancer worldwide, and earlier diagnosis and more effective therapies are required to improve prognosis. As a possible solution, near-infrared fluorescent heptamethine cyanine dyes have been shown to be useful for tumor diagnosis and treatment. Here, we synthesized a novel theranostic agent, IR-817, a multifunctional bioactive small-molecule that has near-infrared emission, targets mitochondria in cancer cells, and has selective anti-cancer effects.

Uncovering the Mechanisms of Active Components from Toad Venom against Hepatocellular Carcinoma Using Untargeted Metabolomics.

Toad venom, a dried product of secretion from Cantor or Schneider, has had the therapeutic effects of hepatocellular carcinoma confirmed. Bufalin and cinobufagin were considered as the two most representative antitumor active components in toad venom. However, the underlying mechanisms of this antitumor effect have not been fully implemented, especially the changes in endogenous small molecules after treatment.

ZWZ-3, a Fluorescent Probe Targeting Mitochondria for Melanoma Imaging and Therapy.

The increased drug resistance and metastasis of melanoma resulted in poor prognosis of patients. Here, we designed and synthesized a novel hemicyanine-based fluorescent probe ZWZ-3, and investigated its application for melanoma imaging and treatment both and . ZWZ-3 preferentially accumulated in melanoma cells a process that depended on the organic anion-transporting polypeptide (OATP), which targeted mitochondria on the hemicyanine cationic nitrogen.

Lipids and Lipid Derivatives for RNA Delivery.

RNA-based therapeutics have shown great promise in treating a broad spectrum of diseases through various mechanisms including knockdown of pathological genes, expression of therapeutic proteins, and programmed gene editing. Due to the inherent instability and negative-charges of RNA molecules, RNA-based therapeutics can make the most use of delivery systems to overcome biological barriers and to release the RNA payload into the cytosol. Among different types of delivery systems, lipid-based RNA delivery systems, particularly lipid nanoparticles (LNPs), have been extensively studied due to their unique properties, such as simple chemical synthesis of lipid components, scalable manufacturing processes of LNPs, and wide packaging capability.

A far-red-emitting fluorescence probe for selective and sensitive detection of no in live cells and in C. elegans.

Nitric oxide (NO), a ubiquitous intracellular and intercellular messenger molecule, plays vital roles in many physiological processes and is closely related to many diseases. Although a lot of fluorescent probes have been developed for real-time detection of NO successfully, the probes still suffer from poor tissue permeability and limited selectivity. In this study, a novel far-red fluorescent probe ZJL-3 based on rhodamine fluorescent dye was designed, synthesized, and used for NO determination.

Redox-sensitive polymeric micelles with aggregation-induced emission for bioimaging and delivery of anticancer drugs.

Background: Nano-drug delivery systems show considerable promise for effective cancer therapy. Polymeric micelles have attracted extensive attention as practical nanocarriers for target drug delivery and controlled drug delivery system, however, the distribution of micelles and the release of the drug are difficult to trace in cancer cells. Therefore, the construction of a redox-sensitive multifunctional drug delivery system for intelligent release of anticancer drugs and simultaneous diagnostic imaging and therapy remains an attractive research subject.

A novel benzoxazinone derivative YLT-LL-11 inhibits diffuse large B-cell lymphoma growth via inducing cell cycle arrest and apoptosis.

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive B-cell non-Hodgkin's lymphoma (NHL) with high treatment difficulty and high relapse rate. The bromodomain and extra-terminal (BET) proteins play significant roles in supporting the transcription of known DLBCL oncogene MYC, which provides a way for the development of targeted therapeutic agents to address this kind of malignant tumor. Here, we reported a novel benzoxazinone derivative YLT-LL-11 as potential BRD4 inhibitor and further investigated the biological activities against DLBCL.

A Polymer Responsive to Reactive Oxygen Species for Safe, Efficient Chemo-Photodynamic Combined Cancer Therapy.

Combining photodynamic therapy (PDT) and chemotherapy can improve anti-cancer efficacy. In this study, a novel copolymer PTPP combining thioketal and protoporphyrin was synthesized and tested for antitumor activity. Self-assembled PTPP micelles loaded with doxorubicin (DOX) showed uniform size, narrow particle size distribution and greater antitumor activity and than DOX-loaded micelles made from the commonly used material mPEG-PCL.

Structural characterization of a Δ, Δ-enoyl-CoA isomerase from Pseudomonas aeruginosa: implications for its involvement in unsaturated fatty acid metabolism.

Gene PA4980 from Pseudomonas aeruginosa encodes a putative enoyl-coenzyme A hydratase/isomerase that is associated with the function of the biofilm dispersion-inducing signal molecule cis-2-decenoic acid. To elucidate the role of PA4980 in cis-2-decenoic acid biosynthesis, we reported the crystal structure of its protein product at 2.39 Å.

Effective combination therapy of percutaneous ethanol injection and chemotherapy based on injectable low molecular weight gels.

Percutaneous ethanol injection (PEI) therapy was used in liver cancer treatment, however, the therapeutic ethanol in PEI easily flew away from injected solid tumours and hinder the treatment effect. In this paper, injectable supramolecular gels formed by self-assembly of low molecular weight gelators (LMWGs) based on glycylglycine modified phenylboronic acid were prepared to localize ethanol and load chemotherapeutic drug for in situ synergistic therapy. The mechanism, morphology and rheological property of supramolecular gels were characterized by NMR, UV, SEM, etc.

A reactive oxygen species (ROS)-responsive low molecular weight gel co-loaded with doxorubicin and Zn(ii) phthalocyanine tetrasulfonic acid for combined chemo-photodynamic therapy.

Low molecular weight gels (LMWGs) have significant advantages in drug delivery such as high drug loading capacity, in situ delivery of drug to the lesion site, sustaining drug release with excellent bioavailability, and minimized side effects. Here, we synthesized a reactive oxygen species (ROS)-responsive gelator to prepare an injectable gel. An anticancer drug, doxorubicin hydrochloride (DOX), and a photosensitizer, Zn(ii) phthalocyanine tetrasulfonic acid (ZnPCS), were loaded into the gel for combined chemo-photodynamic therapy.

A ROS-responsive polymeric micelle with a π-conjugated thioketal moiety for enhanced drug loading and efficient drug delivery.

As the implications of reactive oxygen species (ROS) are elucidated in many diseases, ROS-responsive nanoparticles are attracting great interest from researchers. In this work, a ROS sensitive thioketal (TK) moiety with a π-conjugated structure was introduced into biodegradable methoxy poly(ethylene glycol)-thioketal-poly(ε-caprolactone)mPEG-TK-PCL micelles as a linker, which was designed to speed up the drug release and thus enhance the therapeutic efficacy. The micelle showed a high drug loading content of 12.

Fabrication of Polymeric Micelles with Aggregation-Induced Emission and Forster Resonance Energy Transfer for Anticancer Drug Delivery.

With the aim of obtaining effective cancer therapy with simultaneous cellular imaging, dynamic drug-release monitoring, and chemotherapeutic treatment, a polymeric micelle with aggregation-induced emission (AIE) imaging and a Forster resonance energy transfer (FRET) effect was fabricated as the drug carrier. An amphiphilic conjugate of 1H-pyrrole-1-propanoicacid (MAL)-poly(ethylene glycol) (PEG)-Tripp-bearing AIE molecules were synthesized and self-assembled into micelles to load the anticancer drug doxorubicin (DOX). Spherical DOX-loaded micelles with the mean size of 106 nm were obtained with good physiological stability (CMC, 12.

Near infrared light responsive hybrid nanoparticles for synergistic therapy.

A near infrared (NIR) light responsive chromophore 7-(diethylamino)-4-(hydroxymethyl)-2H-chromen-2-one (DEACM) was synthesized and incorporated to β-cyclodextrins with cRGD functionalized poly(ethylene glycol), the amphiphiles were coordinated with Au nanorods or nanoparticles to load anticancer drug doxorubicin (DOX) for fabricating hybrid nanoparticles. The π-π stacking interaction between DEACM and DOX was formed in the hybrid nanoparticles, which contributed to the high drug loading content. The Au nanorods or nanoparticles enhanced the photosolvolysis of DEACM under the irradiation of NIR with 808 nm wavelength and triggered the accelerated drug release from the nanoparticles.

Intramolecular [1,4]-S- to O-silyl migration: a useful strategy for synthesizing Z-silyl enol ethers with diverse thioether linkages.

An intramolecular [1,4]-S- to O-silyl migration has been used to form silyl enol ethers with Z-configurational control. The silyl migration also creates a new anion center at sulfur, which can subsequently react with electrophiles to generate Z-silyl enol ethers with diverse thioether linkages. The synthetic utility of this pathway was demonstrated by modifying the Z-silyl enol ethers with aldehydes via a Mukaiyama aldol reaction or Prins cyclization to generate functionalized organosulfur compounds.

[1,5]-Anion relay/[2,3]-Wittig rearrangement of 3,3-bis(silyl) allyl enol ethers: synthesis of useful vinyl bis(silane) species.

The [1,5]-anion relay/[2,3]-Wittig rearrangement of 3,3-bis(silyl) enol allyl ethers has been developed. This reaction provides an efficient method to synthesize versatile vinyl bissilanes, which can be transformed into trisubstituted vinylsilanes through a [1,4]-Brook rearrangement/alkylation protocol using a wide range of electrophiles.