Discovery of a Potent Dual Son of Sevenless 1 (SOS1) and Epidermal Growth Factor Receptor (EGFR) Inhibitor for the Treatment of Prostate Cancer.

Multitarget medications represent an appealing therapy against the disease with multifactorial abnormalities─cancer. Therefore, simultaneously targeting son of sevenless 1 (SOS1) and epidermal growth factor receptor (EGFR), two aberrantly expressed proteins crucial for the oncogenesis and progression of prostate cancer, may achieve active antitumor effects. Here, we discovered dual SOS1/EGFR-targeting compounds via pharmacophore-based docking screening. The most prominent compound SE-9 exhibited nanomolar inhibition activity against both SOS1 and EGFR and efficiently suppressed the phosphorylation of ERK and AKT in prostate cancer cells PC-3. Cellular assays also revealed that SE-9 displayed strong antiproliferative activities through diverse mechanisms, such as induction of cell apoptosis and G1 phase cell cycle arrest, as well as reduction of angiogenesis and migration. Further in vivo findings showed that SE-9 potently inhibited tumor growth in PC-3 xenografts without obvious toxicity. Overall, SE-9 is a novel dual-targeting SOS1/EGFR inhibitor that represents a promising treatment strategy for prostate cancer.

Fluorescence determination of quercetin in food samples using polyhedron-shaped MOF@MOF(NUZ-8) based on NH2-UiO-66 and ZIF-8.

A new metal-organic framework compound (MOF@MOF, NUZ-8) comprised of NH2-UiO-66 and ZIF-8 under the polyvinylpyrrolidone (PVP) as the structure modifier was synthesized through an internal extended growth method (IEGM). The resulting NUZ-8 emerged the unreported unique polyhedron shape and showed considerable specific surface area (1466.1862 m2/g), excellent adsorption capacity, and fluorescence. NUZ-8 was used as a probe for the rapid optical detection of natural antioxidant quercetin (QCT). Its outstanding selectivity and sensitivity to QCT are derived from the fact that NH2-UiO-66 acted as an optical tentacle to perceive QCT in virtue of its luminescence advantages, and ZIF-8 realized the selective enrichment of the QCT through its electron-rich framework structure. The experiments were carried out at an excitation wavelength of 335 nm and an emission wavelength range of 370-530 nm. Under conditions of the investigation, this probe realized the rapid detection of QCT and considerable adsorption capacity with wide linearity (0.3-80 µM), a low detection limit (0.14 µM), and acceptable recoveries (84.0-97.0%) in red wine samples, properties which were superior to many other detection platforms. The synthesis and the use of the above polyhedral composite provide guidance for the application of the IEGM in enhancing chemical sensing and instant determination of drugs.Graphical abstract Flow chart of this paper.

Folic acid-conjugated chitosan oligosaccharide-magnetic halloysite nanotubes as a delivery system for camptothecin.

In this research, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemotherapy, folic acid conjugated chitosan oligosaccharides assembled magnetic halloysite nanotubes (FA-COS/MHNTs) have been tailored as multitask drug delivery system towards camptothecin (CPT). Besides magnetic targeting, the nanocomposites have been reacted with folate complex in order to selectively target cancer cells over expressing the folic acid receptor. HNTs showed to have a high storage capacity of CPT. In vitro, the release results indicated that CPT outflow from the nanocarriers at pH 5 was much greater than that at both pH 6.8 and 7.4. MTT assays showed that the CPT-loaded nanocarriers exhibited stronger cell growth inhibitory against colon cancer cell. Furthermore, nanocarriers gained specificity to target cancer cells because of the enhanced cell uptake mediated by FA moiety and presence of COS. Therefore, the rational designed HNTs nanocarrier for chemotherapy drug showed great potential as tumor-targeted drug delivery carrier.

Preparation of multifunctional PEG-graft-Halloysite Nanotubes for Controlled Drug Release, Tumor Cell Targeting, and Bio-imaging.

With the intent of enhancing the loading capacity and controlled the release of a low-water soluble drug (quercetin), 6 ar ms (Poly-Ethylene-Glycol)-amine was grafted in the external surface of halloysite nanotubes. The grafted halloysite nanotubes (HNTs-g-PEG) were decorated with carbon quantum dots for additive fluorescents properties. Conjointly, biotin was conjugated to PEG's free amine groups for precise targeting of tumor tissue and higher cellular uptake. The obtained nanoparticles were characterized by the FTIR, TEM, XRD, zeta potential and TGA analysis. The photoluminescence (PL) properties were investigated by firstly, observing under UV-light at 365 nm; then, the fluorescence spectra of modified HNTs at different levels of preparation were obtained and showed a suitable blue fluorescence. Furthermore, the fluorescent properties were demonstrated by the optical image of HNTs-g-PEG-CDs-Biotin obtained from the confocal microscope, which could be interesting for both in vitro and in vivo imaging. Besides, the prepared NPs showed a superior loading capacity of Que (278.36 mg/g) at optimal adsorption conditions comparing to pristine HNTs. The in vitro drug release from these NPs was relatively sustained and pH sensitive. The incubation of the prepared HNTs-g-PEG-CDs-Biotin NPs with HeLa cells showed a low toxicity and a suitable biocompatibility. The MTT assay of the Que-loaded NPs possesses enhanced antitumor activity over the free Que.

Anticancer loading and controlled release of novel water-compatible magnetic nanomaterials as drug delivery agents, coupled to a computational modeling approach.

The preparation, characterization and application of novel anticancer "epirubicin" (EPI) water-compatible magnetic molecularly imprinted polymers (M-MIPs) like artificial antibodies by computational design and chemical synthesis as a carrier for drug delivery is described herein. Two monomers: methacrylic acid (MAA) and methacrylamide (MAM) were selected by computational simulation from the four chemicals used. Covalent and non-covalent bonds were evaluated by this technique based on the interaction mode and energy with template or solvent. Non-covalent bonding was predominant in all cases and major energy interaction was observed. The nanomaterials were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), and a vibrating sample magnetometer (VSM). The loading and controlled release studies performed showed a slight advantage for the M-MIP obtained from MAA than that from MAM at ambient temperature. However, the drug release in vitro was slightly better for the second M-MIP when the temperature increased to 50 °C. The water-compatible nanomaterial showed good pH-sensitive drug release profiles in vitro. Briefly, due to its magnetic property, amphiphilicity, good biomimetic recognition of EPI, high adsorption capacity and controlled release, the epirubicin M-MIPs synthesized in this study are suitable to be applied to a magnetic targeted drug delivery system.