The Anti-Tumor Effects of M1 Macrophage-Loaded Poly (ethylene glycol) and Gelatin-Based Hydrogels on Hepatocellular Carcinoma
Autor: | X Qi, Yeung Owh, Alberto Daniel Guerra, Kwan Man, Weiyuan John Kao |
---|---|
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Carcinoma Hepatocellular Hepatocellular carcinoma Blotting Western Mice Nude Medicine (miscellaneous) Apoptosis Polyethylene Glycols Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Cell Line Tumor medicine Animals Humans Macrophage Interferon gamma Pharmacology Toxicology and Pharmaceutics (miscellaneous) M1 macrophages Macrophages Liver Neoplasms technology industry and agriculture Hydrogels In vitro Animal Model 030104 developmental biology chemistry 030220 oncology & carcinogenesis Self-healing hydrogels M1 hydrogels Cancer research Gelatin Tumor necrosis factor alpha Ethylene glycol Research Paper medicine.drug |
Zdroj: | Theranostics |
ISSN: | 1838-7640 |
DOI: | 10.7150/thno.20251 |
Popis: | Background and Aims: Recently we reported that direct injection of M1 macrophages significantly caused tumor regression in vivo. Despite the promising result, a major limitation in translating this approach is the induction of acute inflammatory response. To improve the strategy, a biocompatible scaffold for cell presentation and support is essential to control cell fate. Here, we aimed to elucidate the anti-tumor effects of a poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) cross-linked hydrogels capsulated with M1 macrophages in both in vitro and in vivo disease models. Methods: Hydrogels were made at 0.5% (w/v) Iragcure 2959 photoinitiator, 10% (w/v) PEGdA, and 10% (w/v) Gel-PEG-Cys. Monocytic THP-1 cells were loaded into hydrogels and differentiated into M1 macrophages with lipopolysaccharide (LPS) and interferon gamma (IFN-γ). The M1 hydrogels were then cocultivated with HCC cell-lines Hep3B and MHCC97L to investigate the anti-tumor capacities and the associated molecular profiles in vitro. A nude mice ectopic liver cancer model with dorsal window chamber (DWC) and a subcutaneous tumor model were both performed to validate the in vivo application of M1 hydrogels. Results: M1 hydrogels significantly decreased the viability of HCC cells (MHCC97L: -46%; Hep3B: -56.9%; P |
Databáze: | OpenAIRE |
Externí odkaz: |