Double Cell Model Research Articles

Sequential delivery of VEGF siRNA and paclitaxel for PVN destruction, anti-angiogenesis, and tumor cell apoptosis procedurally via a multi-functional polymer micelle

Co-delivery of chemotherapy drugs and VEGF siRNA (siVEGF) to control tumor growth has been a research hotspot for improving cancer treatment. Current systems co-deliver siVEGF and chemo drugs into tumor cells simultaneously. Although effective, these systems do not flow to the abnormal blood vessels around tumor cells (vascular niche, PVN), which play an important role in the metastasis and deterioration of the tumor. Thus, we custom-synthesized triblock copolymer poly(ε-caprolactone)-polyethyleneglycol-poly(L-histidine) (PCL-PEG-PHIS) with previously synthesized folate-PEG-PHIS to construct a targeted multifunctional polymer micelle (PTX/siVEGF-CPPs/TMPM) to sequentially deliver siVEGF-CPPs (disulfide bond-linked siVEGF and cell-penetrating peptides) and paclitaxel (PTX). The sequential delivery vesicles showed the anticipated three-layered TEM structure and dual-convertible (surface charge- and particle size-reversible) features in the tumor environment (pH 6.5), which guaranteed the sequential release of siVEGF-CPPs and PTX in the tumor extracellular environment and tumor cells, respectively. To mimic the in vivo tumor environment, a double cell model was employed by co-culturing HUVECs and MCF-7 cells. Improved cell endocytosis efficiency, VEGF gene silence efficacy, and in vitro anti-proliferation activity were achieved. An in vivo study on MCF-7 tumor-bearing female nude mice also indicated that sequential delivery vesicles could lead to significant induction of tumor cell apoptosis, loss of VEGF expression, and destruction of tumor blood vessels (PVN and neovascularization). These sequential delivery vesicles show potential as an effective co-delivery platform for siVEGF and chemo drugs to improve cancer therapy efficacy.

Permeability Constant of an Assembly of Wetted Spheres

We have theoretically calculated the coefficient of permeability of an assembly of spheres wetted with residual fluid which does not mix with the flowing fluid. The method used is based on a double-cell model, which is an extension of the improved cell model. The results are compared with those obtained from experiments using kerosene, spindle oil and water, and the applicability of the theory is discussed. It is found that the permeability constant is influenced by the ratio of the viscosity of the main stream to that of the remaining fluid. When this ratio exceeds 1.5, the remaining fluid acts as a lubricant, making the main fluid flow easier.

Permeability Constant of an Assembly of Wetted Spheres

We have theoretically calculated the coefficient of permeability of an assembly of spheres wetted with residual fluid which does not mix with the flowing fluid. The method used is based on a double-cell model, which is an extension of the improved cell model. The results are compared with those obtained from experiments using kerosene, spindle oil and water, and the applicability of the theory is discussed. It is found that the permeability constant is influenced by the ratio of the viscosity of the main stream to that of the remaining fluid. When this ratio exceeds 1.5, the remaining fluid acts as a lubricant, making the main fluid flow easier.