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Hydrogels bearing bioengineered mimetic embryonic microenvironments for tumor reversion
Yufang Zhao1, Hongji Yan, Shupei Qiao
1Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, P. R. China.
Journal of Materials Chemistry. B
|April 9, 2020
Summary
Injectable hydrogels mimic embryonic environments to inhibit Nodal signaling, reversing aggressive tumor phenotypes. This novel oncotherapy approach shows promise for breast cancer and melanoma treatment by promoting tumor benign reversion.
Area of Science:
- Biomaterials Science
- Oncology
- Developmental Biology
Background:
- Embryonic microenvironments possess properties that can reverse aggressive tumor phenotypes by inhibiting the Nodal signaling pathway.
- The potential for transplanting these embryonic microenvironments for oncotherapy warrants investigation.
Purpose of the Study:
- To develop an injectable bioactive hydrogel system capable of creating embryonic microenvironments.
- To evaluate the efficacy of this hydrogel system in reversing tumor phenotypes and treating aggressive cancers.
Main Methods:
- Development of an injectable bioactive hydrogel system incorporating Cripto-1 receptor antibodies (2B11) as Nodal signaling antagonists.
- In vitro assessment of hydrogel effects on cancer cell lines (MDA-MB-231, MCF-7) including mitochondrial membrane potential, apoptosis, and invasiveness.
- In vivo evaluation in mouse models of breast cancer and melanoma, analyzing tumor growth, cell morphology transformation, gene expression changes (tumor suppressors and oncogenes) via high-throughput sequencing.
Main Results:
- In vitro studies demonstrated reduced mitochondrial membrane potential, increased apoptosis, and decreased invasiveness of cancer cells.
- In vivo studies showed significant inhibition of tumor growth in both breast cancer and melanoma models.
- The hydrogel system induced phenotypic reversion in melanoma cells and modulated tumor suppressor and oncogene expression, confirming benign tumor reversion.
Conclusions:
- The developed injectable biomaterial system effectively creates a therapeutic microenvironment.
- This approach shows significant potential for treating melanoma and breast cancer by inducing benign tumor phenotype reversion.
