Resveratrol Loaded Liposomes Disrupt Cancer Associated Fibroblast Communications within the Tumor Microenvironment to Inhibit Colorectal Cancer Aggressiveness

Colorectal cancer (CRC) is a cancer-associated fibroblast, CAF-rich tumor. CAF promotes cancer cell proliferation, metastasis, drug resistance via secretes soluble factors, and extracellular matrices which leads to dense stroma, a major barrier for drug delivery. Resveratrol (RES) is a polyphenolic compound, has several pharmacologic functions including anti-inflammation and anticancer effects. Considering tumor microenvironment of CRC, resveratrol-loaded liposome (L-RES) was synthesized and employed to inhibit CAF functions. The L-RES was synthesized by thin-film hydration method. The cytotoxicity of L-RES was evaluated using MTT assay. Effect of L-RES treated CAF on tumor spheroid growth was performed. Cell invasion was determined using spheroid invasion assay. The effect of L-RES on 5-fluorouracil (5-FU) sensitivity of CRC cells was determined in co-cultured tumor spheroids. Subtoxic dose of L-RES was selected to study possible inhibiting CAF functions. Decreased CAF markers, α-SMA and IL-6 levels, were observed in L-RES treated activated fibroblast. Interestingly, the activated fibroblast promoted invasive ability and drug resistance of CRC cells in co-culture condition of both 2D and 3D cultures and was attenuated by L-RES treatment in the activated fibroblast. Therefore, L-RES provides a promising drug delivery strategy for CRC treatment by disrupting the crosstalk between CRC cells and CAF

Inhibiting Metastasis and Improving Chemosensitivity via Chitosan-Coated Selenium Nanoparticles for Brain Cancer Therapy

Selenium nanoparticles (SeNPs) were synthesized to overcome the limitations of selenium, such as its narrow safe range and low water solubility. SeNPs reduce the toxicity and improve the bioavailability of selenium. Chitosan-coated SeNPs (Cs-SeNPs) were developed to further stabilize SeNPs and to test their effects against glioma cells. The effects of Cs-SeNPs on cell growth were evaluated in monolayer and 3D-tumor spheroid culture. Cell migration and cell invasion were determined using a trans-well assay. The effect of Cs-SeNPs on chemotherapeutic drug 5-fluorouracil (5-FU) sensitivity of glioma cells was determined in tumor spheroids. An in vitro blood–brain barrier (BBB) model was established to test the permeability of Cs-SeNPs. SeNPs and Cs-SeNPs can reduce the cell viability of glioma cells in a dose-dependent manner. Compared with SeNPs, Cs-SeNPs more strongly inhibited 3D-tumor spheroid growth. Cs-SeNPs exhibited stronger effects in inhibiting cell migration and cell invasion than SeNPs. Improved 5-FU sensitivity was observed in Cs-SeNP-treated cells. Cellular uptake in glioma cells indicated a higher uptake rate of coumarin-6-labeled Cs-SeNPs than SeNPs. The capability of coumarin-6 associated Cs-SeNPs to pass through the BBB was confirmed. Taken together, Cs-SeNPs provide exceptional performance and are a potential alternative therapeutic strategy for future glioma treatment