Dual pH-Responsive and Tumor-Targeted Nanoparticle-Mediated Anti-Angiogenesis siRNA Delivery for Tumor Treatment.

Purpose: In order to overcome the biological barriers at all levels and enhance the delivery efficiency of siRNA, we have prepared a multifunctional siRNA delivery system (CHCE/siRNA nanoparticles) through self-assembly of the carboxymethyl chitosan modified with histidine, cholesterol, and anti-EGFR antibody (CHCE). Methods: The morphology of CHCE/siRNA NPs was detected by dynamic light scattering and scanning electron microscope. In vitro, we assessed the tumor-targeting, cellular uptake, and endosomal escape by flow cytometry and confocal laser scanning microscopy, confirming the CHCE/siRNA NPs functions in gene silencing and cell killing ability. In vivo, we examined the biodistribution of the CHCE/siRNA NPs by the IVIS imaging system and confirmed the therapeutic effect of NPs in the nude-mouse tumor model. Results: The CHCE/siRNA NPs exhibited nanosized spherical with narrow size distribution. In vitro, the CHCE/siRNA NPs incorporated a dual capability of tumor targeting and pH response that could facilitate cellular bind, cellular uptake, and endosomal escape. The CHCE/siRNA NPs could effectively silence the vascular endothelial growth factor A (VEGFA) to cause cell apoptosis and inhibit proliferation. In vivo, the CHCE/siRNA NPs could target tumor sites to knock down VEGFA and achieve a better anti-tumor effect. Conclusion: We successfully prepared a novel siRNA delivery system with the double capability of tumor targeting and pH response, which can break through the biological barriers to penetrate deep into tumors and achieve better therapeutic tumor effects, providing a new ideal delivery platform for siRNA.

A sesquiterpenoid tropolone and 1,2,3,4-tetrahydronaphthalene derivatives from Olax imbricata roots.

The methanol extract of Olax imbricata roots afforded one new sesquiterpenoid tropolone and three new 1,2,3,4-tetrahydronaphthalene derivatives, olaximbrisides A-D (1-4). Their structures were determined by 1D and 2D NMR experiments in combination of HRESIMS. The relative configurations were assigned by the NOESY experiments. The absolute configurations were established by a combination of X-ray diffraction analysis and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for their cytotoxic effects against some cancer cell lines. Among them, compound 1 exhibited the cytotoxicities against MCF-7, HepG2 and LU cell lines with IC50 values of 16.3, 34.3 and 8.0 µM, respectively.

Cytotoxic Flavones from the Stem Bark of Bougainvillea spectabilis Willd.

Five new flavones possessing a fully substituted A-ring with C-6 and C-8 methyl groups, bougainvinones I - M (1: -5: ), along with three known congeners, 2'-hydroxydemethoxymatteucinol (6: ), 5,7,3',4'-tetrahydroxy-3-methoxy-6,8-dimethylflavone (7: ) and 5,7,4'-trihydroxy-3-methoxy-6,8-dimethylflavone (8: ), were isolated from the EtOAc extract of the stem bark of Bougainvillea spectabilis. Their structures were established by means of spectroscopic data (ultraviolet, infrared, high-resolution electrospray ionization mass spectrometry, and one-dimensional and two-dimensional nuclear magnetic resonance) and single-crystal X-ray crystallographic analysis. The in vitro cytotoxicity of all isolated compounds against five cancer cell lines (KB, HeLa S-3, MCF-7, HT-29, and HepG2) was evaluated. Compound 5: showed promising cytotoxic activity against the KB and HeLa S-3 cell lines, with IC50 values of 7.44 and 6.68 µM. The other compounds exhibited moderate cytotoxicity against the KB cell line.