Folate receptor-mediated delivery system based on chitosan coated polymeric nanoparticles for combination therapy of breast cancer.

Combination therapy using two or more drugs with different mechanisms of action is an effective strategy for treating cancer. This is because of the synergistic effect of complementary drugs that enhances their effectiveness. However, this approach has some limitations, such as non-specific distribution of the drugs in the tumor and the occurrence of dose-dependent toxicity to healthy tissues. To overcome these issues, we have developed a folate receptor-mediated co-delivery system that improves the access of chemotherapy drugs to the tumor site. We prepared a nanoplatform by encapsulating paclitaxel (PTX) and curcumin (CUR) in poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) (PCL-PEG-PCL) co-polymer using a double emulsion method and coating nanoparticles with pH-responsive chitosan-folic acid (CS-FA) conjugate. The nanocarrier's physicochemical properties were studied, confirming successful preparation with appropriate size and morphology. PTX and CUR could be released synchronously in a controlled and acid-facilitated manner. The dual drug-loaded nanocarrier exhibited excellent anti-tumor efficiency in MDA-MB-231 cells in vitro. The active targeting effect of FA concluded from the high inhibitory effect of dual drug-loaded nanocarrier on MDA-MB-231 cells, which have overexpressed folate receptors on their surface, compared to Human umbilical vein endothelial cells (HUVEC). Overall, the nanoengineered folate receptor-mediated co-delivery system provides great potential for safe and effective cancer therapy.

Harnessing rat derived model cells to assess the toxicity of TiO2 nanoparticles.

Until now, a few studies have been conducted on the destructive effects of TiO2 NPs in living organisms, and studies on the toxicity of TiO2 NPs are still in the beginning phases. Because of the widespread use of TiO2 NPs in all areas of human life, it is essential to study their profound and fundamental toxic effects on each organ and body cell. Herein, we evaluate the effect of exposure to TiO2 NPs on in vitro models derived from the rat bone marrow and adipose tissues. Exposure to TiO2 NPs at 100 and 200 µg/ml exhibited cytotoxicity for the rat bone marrow mesenchymal stem cells (rBMSCs) and rat adipose mesenchymal stem cells (rATSC), respectively. Additionally, reduced rBMSCs and rATSCs frequencies in the S phase of the cell cycle. Moreover, TiO2 NPs enhanced the activity of cellular senescence-associated ß-galactosidase in both model cells. Significantly higher relative expression of aging-related genes P53 and NF-kB (p < 0.05) and lower expression levels of anti-aging-related genes Nanog and SIRT1 were found in the treated cells (p < 0.05). Colony-forming and DAPI staining showed the reduction of cell growth and DNA damage in both rBMSCs and rATSCs. Our findings along with other similar findings showed that TiO2 NPs probably have negative effects on the cell growth, prompt the cells for entry into proliferation stop, DNA damage, and trigger the aging process. Graphical abstract.

Liver bioengineering: Recent trends/advances in decellularization and cell sheet technologies towards translation into the clinic.

Development of novel technologies provides the best tissue constructs engineering and maximizes their therapeutic effects in regenerative therapy, especially for liver dysfunctions. Among the currently investigated approaches of tissue engineering, scaffold-based and scaffold-free tissues are widely suggested for liver regeneration. Analogs of liver acellular extracellular matrix (ECM) are utilized in native scaffolds to increase the self-repair and healing ability of organs. Native ECM analog could improve liver repairing through providing the supportive framework for cells and signaling molecules, exerting normal biomechanical, biochemical, and physiological signal complexes. Recently, innovative cell sheet technology is introduced as an alternative for conventional tissue engineering with the advantage of fewer scaffold restrictions and cell culture on a Thermo-Responsive Polymer Surface. These sheets release the layered cells through a temperature-controlled procedure without enzymatic digestion, while preserving the cell-ECM contacts and adhesive molecules on cell-cell junctions. In addition, several novelties have been introduced into the cell sheet and decellularization technologies to aid cell growth, instruct differentiation/angiogenesis, and promote cell migration. In this review, recent trends, advancements, and issues linked to translation into clinical practice are dissected and compared regarding the decellularization and cell sheet technologies for liver tissue engineering.