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The synthesis of new C60 fullerene derivatives functionalized with thiophene moieties as well as with electron donating or electron withdrawing groups, bromine (Br) or cyano (CN), respectively, using Bingel reactions is reported. The synthesized derivatives were used as the electron transporting materials (ETMs) in inverted perovskite solar cells (PSCs). Compared to devices fabricated with [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM), the new derivatives showed similar electrochemical properties and electron mobilities. However, PSCs based on the new derivatives synthesized in this work exhibited higher power conversion efficiencies (PCEs) than PC61BM based devices, which were ascribed to their better passivation ability, likely due to specific interactions between the fullerene addend and the perovskite layer surface. Devices based on the fullerene bearing the CN group exhibited an additionally improved efficiency due to the increased dielectric constant (εr) of this derivative. These results show that the new functionalized fullerene derivatives can act as efficient ETMs in inverted PSCs. [ABSTRACT FROM AUTHOR]

Abstract: As an integrin α 5 β 1 antagonist, N-acetyl-proline-histidine-serine-cysteine-asparagine-amide (Ac-PHSCN-NH2) is currently in phase II trials for various cancer therapies. In this study Ac-PHSCNK-NH2 (PHSCNK) was used as a novel homing peptide to prepare ligand-targeted liposomes loaded with doxorubicin (PHSCNK-PL-DOX), with the hypothesis that the therapy target of integrin α 5 β 1 may also serve as a delivery target. The stealth liposomes loaded with doxorubicin (PL-DOX) were used as the control. PHSCNK-PL-DOX demonstrated an enhanced intracellular uptake and a greater cytotoxicity against melanoma B16F10 cells in comparison with PL-DOX. The novel targeted formulation displayed stronger tumor inhibition and prolonged survival time in comparison with controls in C57BL/6 mice bearing B16F10 tumors, and it exhibited less heart toxicity in hematoxylin-eosin (H&E) staining of tissues. Taking the pharmacokinetics and biodistribution results into account, the authors conclude that α 5 β 1 integrin-mediated liposomes might be used as a potential delivery system for targeted tumor therapy. From the Clinical Editor: Lactosyl-norcantharidin TMC nanoparticles were found superior in comparison with Lac-NCTD and Lac-NCTD chitosan nanoparticles from the standpoint of antitumor activity on murine hepatocarcinoma 22 subcutaneous model. [Copyright &y& Elsevier]

On the basis of the fact of the overexpression of integrins in malignant tumor cells and neovasculature, and the advantage of polymeric micelles (PM) as the drug carriers, a cyclic RGD peptide (cRGDyK) was anchored on the surface of polyethylene glycol- b-poly(lactic-co-glycolic acid) (PEG- b-PLGA) micelles as a ligand of integrins in order to enhance the intracellular delivery of encapsulated hydrophobic drug into the tumor cells and its neovasculature. Toward this goal, PEG- b-PLGA micelles without or with cRGDyK conjugation loaded with paclitaxel (PTX) or DiI were prepared and characterized. The results revealed that drug-loaded micelles were stable in solution, with small diameters (<80 nm) and a low critical micelle concentration. Spectrophotofluorometry, confocal microscopy, and flow cytometry showed that cRGDyK-conjugated micelles (TPM) facilitated the cell-specific uptake of DiI into the murine melanoma B16-F10 cells and human umbilical vein endothelial cells (HUVEC) via integrin-mediated endocytosis compared with cRGDyK-free micelles (NPM), and the uptake was proportional to the ratio of cRGDyK modification in certain range. Meanwhile, PTX-loaded TPM displayed higher cytotoxicity and antiproliferation activities against both cells than PTX-loaded NPM. These results suggest that cRGDyK-coupled PEG- b-PLGA micelles may be the promising intracellular targeting carriers for efficient delivery of chemotherapeutic agents into tumor cells and neovasculature. [ABSTRACT FROM AUTHOR]

The aim of this study was to prepare a liposome system targeting to both tumor angiogenesis and tumor cells, and to achieve the proof-of-principle. ATN-161 ( N-acetyl-proline-histidine-serine-cysteine-asparagine-amide, PHSCN) is a ligand of integrin α5β1 which is the receptor overexpressed on tumor neovasculature and some tumor cells. In this study, doxorubicin (DOX) was used as the model drug, and a derivative of PHSCN, N-acetyl-proline-histidine-serine-cysteine-asparagine-lysine (amide)-COOH (PHSCNK), was firstly coupled to the surface of PEGylated DOX liposomes (PL-DOX) by a novel approach to obtain the PHSCNK-modified and DOX-loaded PEGylated liposomes (PHSCNK-PL-DOX). These two vehicles were less than 100 nm in average, negatively charged and rather stable at 4°C or 25°C, while they exhibited similar release kinetics in vitro. Cell-specific uptake and cytotoxicity were investigated on human umbilical vein endothelial cells and breast cancer cells by confocal microscopy and sulforhodamine B (SRB) assay. It was found that PHSCNK-PL-DOX significantly enhanced the cell uptake and cytotoxicity of DOX on both cell lines, due to the integrin-mediated endocytosis. It was concluded that, PHSCNK-PL-DOX, which can actively delivery the drug into both tumor neovasculature and tumor cells, may be a promising targeted delivery system for anticancer drug. [ABSTRACT FROM AUTHOR]

Water-insoluble drugs such as paclitaxel (PTX) face a huge challenge for clinical applications due to their low aqueous solubility. In this study, uniform-sized poly ( dl -lactic acid) (PLA), poly( dl -lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol-co-lactide acid) (PELA) microspheres containing PTX were prepared by premix membrane emulsification technique integrated with solvent evaporation method. The different hydrophobicity of polymer led to different distribution and crystal morphology of PTX in microspheres, which further resulted in different loading and encapsulation efficiency, release profile in vitro and cytotoxicity. The PLGA microspheres showed the highest loading and encapsulation efficiency of PTX (5.15%, 70.46%), followed by PLA microspheres (4.33%, 64.33%), together with PELA microspheres (3.35%, 56.68%). The results of PTX release profile in vitro suggested that PLGA and PELA microspheres achieved a more rapid release rate than PLA microspheres due to their hydrophilic property. The antitumor activity in vitro was also evaluated by Lewis Lung Cells (LLC). The PTX-PLGA microspheres exhibited excellent antitumor activity compared with PLA and PELA microspheres, even much better than Taxol®. Therefore, the PLGA microspheres show great potential in application as delivery carriers for water-insoluble drugs, PTX and others. [ABSTRACT FROM AUTHOR]

Changes in the levels of lipid sn -positional isomers are associated with perturbation of the physiological environment within the biological system. Consequently, knowing the concentrations of these lipids holds significant importance for unraveling their involvement in disease diagnosis and pathological mechanisms. However, existing methods for lipid quantification often fall short in accuracy due to the structural diversity and isomeric forms of lipids. To address this challenge, we have developed an aziridine-based isobaric tag labeling strategy that allows (i) differentiation and (ii) enhanced relative quantification of lipid sn -positional isomers from distinct samples in a single run. The methodology enabled by aziridination, isobaric tag labeling, and lithiation has been applied to various phospholipids, enabling the determination of the sn -positions of fatty acyl chains and enhanced relative quantification. The analysis of Escherichia coli lipid extracts demonstrated the enhanced determination of the concentration ratios of lipid isomers by measuring the intensity ratios of mass reporters released from sn -positional diagnostic ions. Moreover, we applied the method to the analysis of human colon cancer plasma. Intriguingly, 17 PC lipid sn -positional isomers were identified and quantified simultaneously, and among them, 7 showed significant abundance changes in the colon cancer plasma, which can be used as potential plasma markers for diagnosis of human colon cancer., Competing Interests: The authors declare the following competing financial interest(s): The authors have submitted a patent application (PCT International Application, PCT/US2022/023580) protecting the methodology described in this article., (© 2024 The Authors. Published by American Chemical Society.)

Microdroplet chemistry is attracting increasing attention for accelerated reactions at the solution-air interface. We report herein a voltage-controlled interfacial microreactor that enables acceleration of electrochemical reactions which are not observed in bulk or conventional electrochemical cells. The microreactor is formed at the interface of the Taylor cone in an electrospray emitter with a large orifice, thus allowing continuous contact of the electrode and the reactants at/near the interface. As a proof-of-concept, electrooxidative C-H/N-H coupling and electrooxidation of benzyl alcohol were shown to be accelerated by more than an order of magnitude as compared to the corresponding bulk reactions. The new electrochemical microreactor has unique features that allow i) voltage-controlled acceleration of electrochemical reactions by voltage-dependent formation of the interfacial microreactor; ii) "reversible" electrochemical derivatization; and iii) in situ mechanistic study and capture of key radical intermediates when coupled with mass spectrometry., (© 2020 Wiley-VCH GmbH.)

The synthesis of new C 60 fullerene derivatives functionalized with thiophene moieties as well as with electron donating or electron withdrawing groups, bromine (Br) or cyano (CN), respectively, using Bingel reactions is reported. The synthesized derivatives were used as the electron transporting materials (ETMs) in inverted perovskite solar cells (PSCs). Compared to devices fabricated with [6,6]-phenyl-C 61 -butyric acid methyl ester (PC 61 BM), the new derivatives showed similar electrochemical properties and electron mobilities. However, PSCs based on the new derivatives synthesized in this work exhibited higher power conversion efficiencies (PCEs) than PC 61 BM based devices, which were ascribed to their better passivation ability, likely due to specific interactions between the fullerene addend and the perovskite layer surface. Devices based on the fullerene bearing the CN group exhibited an additionally improved efficiency due to the increased dielectric constant ( ε r ) of this derivative. These results show that the new functionalized fullerene derivatives can act as efficient ETMs in inverted PSCs., Competing Interests: Conflict of interest There are no conflicts to declare.

First-generation epidermal growth factor receptor (EGFR) inhibitors, gefitinib and erlotinib, have achieved initially marked clinical efficacy for nonsmall cell lung cancer (NSCLC) patients with EGFR activating mutations. However, their clinical benefit was limited by the emergence of acquired resistance mutations. In most cases (approximately 60%), the resistance was caused by the secondary EGFR T790M gatekeeper mutation. Thus, it is still desirable to develop novel third-generation EGFR inhibitors to overcome T790M mutation while sparing wild-type (WT) EGFR. Herein, a series of pyrimido[4,5- d]pyrimidine-2,4(1 H,3 H)-dione derivatives were designed and synthesized, among which the most potent compound 20g not only demonstrated significant inhibitory activity and selectivity for EGFR L858R/T790M and H1975 cells in vitro but also displayed outstanding antitumor efficiency in H1975 xenograft mouse model. The encouraging mutant-selective results at both in vitro and in vivo levels suggested that 20g might be used as a promising lead compound for further structural optimization as potent and selective EGFR L858R/T790M inhibitors.