An analytical method based on high-performance liquid chromatography separation with diode array detection was developed and validated for the synchronised determination of chlorogenic acid and five flavonoids (rutin, isoquercitrin, quercitrin, quercetin, and luteolin) in mulberry leaves (Morus spp.). Chromatographic separation was carried out under gradient elution conditions on a Shim Pack VP-ODS C18 (250 × 4.6 mm, particle size 5 μm) column at a temperature of 30 °C using a mobile phase consisting of 0.5% (v/v) phosphoric acid in water and acetonitrile at a flow rate of 0.9 ml/min. The column eluent process was best at 330 nm (for chlorogenic acid, quercitrin, and luteolin), 350 nm (for rutin and isoquercitrin), and 365 nm (for quercetin). Application of optimum extraction conditions led to extraction of chlorogenic acid and five flavonoids from mulberry leaves with mean recoveries of 97.78-103.24%. The developed method was validated in terms of linearity, recovery, precision, and stability. The relative standard deviation for intra-day precision (n=6) and inter-day precision (n=6) was <1.45%. The optimised protocol provides a simple, sensitive and reproducible method for quantitative analysis of chlorogenic acid and flavonoids from mulberry leaves and may further be explored for other natural products.
Tumor-specific phototheranostics is conducive to realizing precise cancer therapy. Herein, a novel tumor microenvironment (TME)-responsive phototheranostic paradigm based on the combination of semiconducting polymer brushes and polyoxometalate clusters (SPB@POM) is rationally designed. The acidic TME could drive the self-assembly of SPB@POM into bigger aggregates for enhanced tumor retention and accumulation, while the reducing TME could significantly enhance the NIR absorption of SPB@POM for significant improvement of photoacoustic imaging contrast and photothermal therapy efficacy. Therefore, the smart pH/glutathione (GSH)-responsive SPB@POM allows for remarkable phototheranostic enhancement under the unique TME, which has potential for precise tumor-specific phototheranostics with minimal side effects.
Folate receptor (FR) has proven to be a valuable target for chemotherapy using folic acid (FA) conjugates.However, FA-conjugated chemotherapeutics still have low therapeutic efficacy accompanied with side effects, resulting from complications such as short circulation half-life, limited tumor delivery, as well as high kidney accumulation.Herein, we present a novel FA-conjugated paclitaxel (PTX) prodrug which was additionally conjugated with an Evans blue (EB) derivative for albumin binding.The resulting bifunctional prodrug prolonged blood circulation, enhanced tumor accumulation, and consequently improved tumor therapeutic efficacy.Methods: Fmoc-Cys(Trt)-OH was coupled onto PTX at the 7'-OH position for further synthesis of ester prodrug FA-PTX-EB.The targeting ability was investigated using confocal microscopy and flow cytometry.The pharmacokinetics of this bifunctional compound was also studied.Meanwhile, cell viability was evaluated in normal cells and three cancer cell lines by MTT assay.In vivo therapeutic effect was tested on FR-α overexpressing MDA-MB-231 tumor model.Results: Compared with free PTX, the FA-PTX, PTX-EB and FA-PTX-EB prodrugs increased circulation half-life in mice from 2.19 to 3.82, 4.41, and 7.51 h, respectively.Pharmacokinetics studies showed that the FA-PTX-EB delivered more PTX to tumors than FA-PTX and free PTX.In vitro and in vivo studies demonstrated that FA-EB-conjugated PTX induced potent antitumor activity.Conclusion: FA-PTX-EB showed prolonged blood circulation, enhanced drug accumulation in tumors, higher therapeutic index, and lower side effects than either free PTX or monofunctional FA-PTX and EB-PTX.The results support the potential of using EB for the development of long-acting therapeutics.
We developed an efficient palladium-catalyzed fluorosulfonylation reaction of aryl thianthrenium salts to smoothly prepare various aryl sulfonyl fluorides using cheap Na2S2O4 as a convenient sulfonyl source in combination with N-fluorobenzenesulfonimide (NFSI) as an ideal fluorine source under mild reduction conditions. A one-pot synthesis of aryl sulfonyl fluorides starting from various arenes was established as well without the need for separating aryl thianthrenium salts. The practicality of this protocol was demonstrated by gram-scale synthesis, derivatization reactions, and excellent yields.
Compound Fengshiding capsule (CFC), is a Chinese formulation from herbal origin including Alangium platanifolium, Angelicae dahurica, Cynanchum paniculatum and Glycyrrhiza uralensis. CFC is widely used as clinical therapy against rheumatoid arthritis. However, its exact mechanism of action has not been explored yet.In order to explore the synergistic mechanism of CFC, we designed a study adopting network pharmacology scheme to screen the action targets in relation to the CFC components. The study analyses target facts of salicin, paeonol, liquiritin and imperatorin from PubMed database, and explores the potential pharmacological targets of rheumatoid arthritis, cervical neuralgia and sciatica related diseases for their interaction.The results of boosted metabolic pathway showed that the chemical components of CFC interrupted many immune-related pathways, thus participating in immunity regulation of the body and playing a role in the treatment of rheumatism. Collectively, CFC has apoptotic, oxidative stress modulatory and anti-inflammatory effects that accumulatively serve for its clinical application against rheumatoid arthritis.Conclusively, our findings from present study reconnoiters and compacts systematic theoretical approach by utilizing the network pharmacology mechanism of four effective components for the treatment of rheumatism indicating sufficient potential drug targets associated with CFC against rheumatism. These interesting findings entreaties for further in vitro and in vivo studies on the mechanism of compound active ingredient against rheumatism.
Background: Targeted prodrug has various applications as drug formulation for tumor therapy. Therefore, amphoteric small-molecule prodrug combined with nanoscale characteristics for the self-assembly of the nano-drug delivery system (DDS) is a highly interesting research topic. Methods and Results: In this study, we developed a prodrug self-assembled nanoplatform, 2-glucosamine-fluorescein-5(6)-isothiocyanate-glutamic acid-paclitaxel (2DA-FITC-PTX NPs) by integration of targeted small molecule and nano-DDS with regular structure and perfect targeting ability. 2-glucosamine (DA) and paclitaxel were conjugated as the targeted ligand and anti-tumor chemotherapy drug by amino acid group. 2-DA molecular structure can enhance the targeting ability of prodrug-based 2DA-FITC-PTX NPs and prolong retention time, thereby reducing the toxicity of normal cell/tissue. The fluorescent dye FITC or near-infrared fluorescent dye ICG in prodrug-based DDS was attractive for in vivo optical imaging to study the behavior of 2DA-FITC-PTX NPs. In vitro and in vivo results proved that 2DA-FITC-PTX NPs exhibited excellent targeting ability, anticancer activity, and weak side effects. Conclusion: This work demonstrates a new combination of nanomaterials for chemotherapy and may promote prodrug-based DDS clinical applications in the future. Keywords: targeted prodrug, nanoplatform, NIR imaging, chemotherapy
AbstractA visible-light-mediated fluorosulfonylation reaction of thianthrenium salts has been developed to prepare various sulfonyl fluorides with 1,4-diazabicyclo [2.2.2] octane bis (sulfur dioxide) (DABSO) as sulfonyl source and cheap KHF2 as fluorine source based on radical sulfur dioxide insertion and fluorination strategy. This operationally simple protocol proceeds with high functional-group tolerance under mild reaction conditions.Keywords: Fluorosulfonylationthianthrenium saltsvisible-light-mediated Disclosure statementNo potential conflict of interest was reported by the author(s).Additional informationFundingThe authors gratefully acknowledge the financial support from the National Natural Science Foundation of China [No. 21871283], the project of Science and Technology Commission of Shanghai Municipality in China [21010503800], Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai Engineering Research Center of Green Fluoropharmaceutical Technology, and the Science Research Foundation of Shanghai Institute of Technology.
Featured with a large surface area, uniform interpenetrating mesopores, diverse organic framework hybridization, and well-defined surface properties, the hollow mesoporous organosilica nanoparticle (HMON) represents a promising paradigm in drug delivery systems with excellent biocompatibility. However, effective tumor accumulation and precise cancer theranostics of the HMON still remain a challenge. In this study, an "ammonia-assisted hot water etching" method is applied for the successful construction of sub-50 nm thioether/phenylene dual-hybridized HMON with low hemolytic effect. Particularly, the surface modification with Mo(VI)-based polyoxometalate (POM) clusters drives the self-assembly of HMON in the mild acidic tumor microenvironment (TME) to achieve enhanced tumor retention and accumulation. More importantly, the reducibility-activated Mo(VI)-to-Mo(V) conversion within POM not only endows the POM-anchored HMON with outstanding TME-responsive photoacoustic (PA) imaging contrast and photothermal therapy (PTT) performance but also plays an indispensable role in controllably triggering the decomposition of the Mn2(CO)10 payload for CO release, which gives rise to remarkable synergistic PTT-enhanced CO gas therapy for complete tumor eradication. By harnessing the unique acidic and redox properties of TME, the judiciously designed smart POM-anchored HMON nanoplatform is expected to act as a "magic bomb" to selectively destroy cancer without damaging normal tissues. This nanoplatform holds significant potential in realizing TME-responsive self-assembly for enhanced tumor accumulation and precise tumor-specific synergistic therapy, which is very promising for clinical translation.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
