Biology subjects

Moroishi, K.

Publications and source records attributed to Moroishi, K..

3 recordsLinked to original sources

bioRxiv2025

Differentiation of THP-1 Cells in 3D Cancer-Stromal Tissue by Collagen Microfiber for Replicating of Tumor Microenvironment

Abstract textIn three-dimensional (3D) cancer tissue models, the low solubility of type I collagen (Col I) is a limitation in reproducing cancer tissue with high collagen density. we previously reported a "sedimentation culture method" using collagen microfibers (CMF) homogenized Col I powder. This 3D cancer tissue model is expected to reproduce tumor microenvironment comparable to that in tumors bearing mice owing to its high collagen density. However, this 3D cancer tissue model including immune cells such as macrophages has not been reported. In this study, we fabricated a 3D culture system including normal human dermal fibroblasts, human umbilical vein endothelial cells, and cancer cells human monocytes cell line; THP-1 cells by sedimentation culture using CMF. 3D cancer tissue models co-cultured with human colorectal cancer cells for 5 days increased the expression levels of CD14 and CD206, markers of macrophages and M2 macrophages, in THP-1 cells, suggesting differentiation induction toward macrophages and polarization toward M2-like macrophages. We could also demonstrate the applicability of drug efficacy evaluation systems by evaluating the cytotoxicity of poly(vinyl alcohol)-ursodeoxycholic acid15 that induce cell death in response to weak acidic tumor microenvironment in 3D cancer tissue models with macrophages. This 3D cancer tissue models with macrophages are expected to be applied as tools for evaluating the efficacy of cancer therapeutic molecules and for understanding in detail the behavior of immune cells within the tumor microenvironment.

bioengineering↗

bioRxiv2025

Escape from Cell Uptake: Drug-Free Cancer Therapeutics Regulated Hydrophobicity and Negative Charge

Self-aggregation and inducing cell membrane disruption in response to tumor microenvironment-stimuli is expected to be a promising approach for cancer treatment, but is limited by its insufficient stimuli-responsive cytotoxicity due to a lack of in-depth understanding of molecular characteristics, resulting in low selectivity of cell death induction. In this study, we focused on engineering polymer aggregation in detail to further improve tumor microenvironment-responsive cytotoxicity. PVA-U with grafting degrees (G.D.) of 3% (PVA-U3), 15% (PVA-U15), and 25% (PVA-U25) were synthesized and their aggregation properties cytotoxicity was evaluated. The difference in half maximal inhibitory concentration (IC50) values between pH 7.4 and pH 6.5 for PVA-U15 was 4.3-fold, which was greater than that of PVA-U25 at 2.8-fold, suggesting that tumor microenvironment-responsive cytotoxicity could be regulated by controlling G.D. of UDCA. Interestingly, PVA-U15 formed aggregates in the pericellular environment and adsorbed on the cell, effectively inducing cell death whereas PVA-U3 and PVA-U25 showed internalization in the cell. These results indicated that the balance of the surface charge and hydrophobicity could contribute to the adsorption on the cell membrane. These findings are expected to contribute to the development of membrane disruption strategies to control the aggregation properties and cell membrane interaction. Table of ContentsCancer therapeutics strategy targeting tumor microenvironment and cell adsorption of PVA-U with varying granting degree (G.D.). PVA-U is expected to aggregate and disrupt cell membrane in response to tumor microenvironment. PVA-U could regulate cell membrane adsorption by its negative charge and hydrophobicity due to controlling G.D. of UDCA, resulting in optimized tumor microenvironment selectivity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/671160v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@e8d4acorg.highwire.dtl.DTLVardef@1e27a1borg.highwire.dtl.DTLVardef@1beb5d8org.highwire.dtl.DTLVardef@1948d51_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2022

Fabrication of Molecular Blocks with High Responsiveness to the Cancer Microenvironment by Ursodeoxycholic Acid

In cancer therapy, drug delivery system (DDS) has been widely studied to achieve selective drug accumulation at the tumor site. However, DDS still has a major drawback in that it requires multi-step processes for intracellular delivery, resulting in low efficiency of drug delivery. To overcome this problem, we recently reported a molecular block (MB) that disrupts cancer cell membranes in the cancer microenvironment using deoxycholic acid (DCA). However, the MB showed considerable cytotoxicity even at neutral pH possibly due to the structural hydrophobic property of DCA. Herein, we focused on selecting the most suitable bile acid for an MB that possessed high responsiveness to the cancer microenvironment without cytotoxicity at neutral pH. Cell viabilities of the free bile acids such as DCA, chenodeoxycholic acid (CDCA), cholic acid (CA) and ursodeoxycholic acid (UDCA) were evaluated at neutral pH (pH = 7.4) and a cancer acidic environment (pH = 6.3 [~] 6.5). The half-maximal inhibition concentration (IC50) value of UDCA at pH = 7.4 showed an approximately 7.5-fold higher IC50 value than that at pH = 6.3, whereas the other bile acids yielded less than a 4-fold IC50 value difference between the same pHs. Biocompatible poly(vinyl alcohol) (PVA) was functionalized with UDCA (PVA-UDCA) for synthesis of higher responsiveness to the cancer microenvironment without cytotoxicity at neutral pH. Importantly, 56% pancreatic cancer cell death was observed at pH = 6.5, whereas only 10% was detected at neutral pH by the PVA-UDCA treatment. However, PVA-DCA indicated almost the same cancer cell death property independent of pH condition. These results suggest PVA-UDCA shows great potential for a new class of MB.

bioengineering↗