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Article: The Anti-Tumor Effects of M1 Macrophage-Loaded Poly (ethylene glycol) and Gelatin-Based Hydrogels on Hepatocellular Carcinoma
Title | The Anti-Tumor Effects of M1 Macrophage-Loaded Poly (ethylene glycol) and Gelatin-Based Hydrogels on Hepatocellular Carcinoma |
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Authors | |
Issue Date | 2017 |
Publisher | Ivyspring International Publisher. The Journal's web site is located at http://www.thno.org/ |
Citation | Theranostics, 2017, v. 7 n. 15, p. 3732-3744 How to Cite? |
Abstract | 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<0.05) compared to the control in vitro. In response to HCC cells, the hydrogel embedded M1 macrophages up-regulated nitrite and tumor necrosis factor alpha (TNF-α) activating caspase-3 induced apoptosis in the tumor cells. Increased tumor necrosis was observed in DWC filled with M1 hydrogels. In addition, mice treated with M1 hydrogels exhibited a significant 2.4-fold decrease in signal intensity of subcutaneous HCC tumor compared to control (P=0.036). Conclusion: M1 hydrogels induced apoptosis in HCC cells and tumor regression in vivo. Continuous development of the scaffold-based cancer immunotherapy may provide an alternative and innovative strategy against HCC. |
Persistent Identifier | http://hdl.handle.net/10722/248580 |
ISSN | 2023 Impact Factor: 12.4 2023 SCImago Journal Rankings: 2.912 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Guerra, AG | - |
dc.contributor.author | Yeung, WH | - |
dc.contributor.author | Qi, X | - |
dc.contributor.author | Kao, WJ | - |
dc.contributor.author | Man, K | - |
dc.date.accessioned | 2017-10-18T08:45:23Z | - |
dc.date.available | 2017-10-18T08:45:23Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Theranostics, 2017, v. 7 n. 15, p. 3732-3744 | - |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | http://hdl.handle.net/10722/248580 | - |
dc.description.abstract | 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<0.05) compared to the control in vitro. In response to HCC cells, the hydrogel embedded M1 macrophages up-regulated nitrite and tumor necrosis factor alpha (TNF-α) activating caspase-3 induced apoptosis in the tumor cells. Increased tumor necrosis was observed in DWC filled with M1 hydrogels. In addition, mice treated with M1 hydrogels exhibited a significant 2.4-fold decrease in signal intensity of subcutaneous HCC tumor compared to control (P=0.036). Conclusion: M1 hydrogels induced apoptosis in HCC cells and tumor regression in vivo. Continuous development of the scaffold-based cancer immunotherapy may provide an alternative and innovative strategy against HCC. | - |
dc.language | eng | - |
dc.publisher | Ivyspring International Publisher. The Journal's web site is located at http://www.thno.org/ | - |
dc.relation.ispartof | Theranostics | - |
dc.rights | Theranostics. Copyright © Ivyspring International Publisher. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | The Anti-Tumor Effects of M1 Macrophage-Loaded Poly (ethylene glycol) and Gelatin-Based Hydrogels on Hepatocellular Carcinoma | - |
dc.type | Article | - |
dc.identifier.email | Yeung, WH: why21@hku.hk | - |
dc.identifier.email | Qi, X: qixiang515@connect.hku.hk | - |
dc.identifier.email | Kao, WJ: wjkao@hku.hk | - |
dc.identifier.email | Man, K: kwanman@hku.hk | - |
dc.identifier.authority | Kao, WJ=rp02076 | - |
dc.identifier.authority | Man, K=rp00417 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.7150/thno.20251 | - |
dc.identifier.scopus | eid_2-s2.0-85028377598 | - |
dc.identifier.hkuros | 279712 | - |
dc.identifier.volume | 7 | - |
dc.identifier.issue | 15 | - |
dc.identifier.spage | 3732 | - |
dc.identifier.epage | 3744 | - |
dc.identifier.isi | WOS:000408444200009 | - |
dc.publisher.place | Australia | - |
dc.identifier.issnl | 1838-7640 | - |