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Collagen Hydrogel Functionalized with Collagen-Targeting IFNA2b Shows Apoptotic Activity in Nude Mice with
Jun-Gen Hu1, Jin-Kui Pi1, Yan-Lin Jiang1
1Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 1, Keyuan Fourth Road, Chengdu, Sichuan 610041, P. R. China.
Abstract:
Interferon alpha 2b (IFNA2b) has been used in immunotherapy for cancers with certain success. To reduce fast diffusion of IFNA2b and consequent dose-dependent side effects, we constructed a collagen hydrogel loaded with IFNA2b fused to collagen-binding domain by using methods of tissue engineering. The fusion protein showed apoptotic activity similar to that of native IFNA2b against MCF-7 cells in vitro, but with relatively higher affinity for collagen type I. Accordingly, the former diffused out of the collagen matrix slower than the latter. Importantly, collagen hydrogels loaded with the fusion protein possessed apoptotic activity in vitro and released the engineered cytokine in a controlled manner. In addition, such hydrogels reduced tumor size and extended the survival of the mouse model with xenografted tumors, which suggested a moderate antitumor activity in vivo.
Insights
This study engineered a collagen hydrogel to control the release of Interferon alpha 2b (IFNA2b) for cancer immunotherapy. The novel hydrogel demonstrated controlled release, reduced tumor size, and extended survival in mice.
Area of Science:
- Biotechnology
- Cancer Research
- Immunotherapy
Background:
- Interferon alpha 2b (IFNA2b) is an immunotherapy agent for cancer.
- Rapid diffusion of IFNA2b causes dose-dependent side effects.
- Controlled delivery systems are needed to improve IFNA2b efficacy.
Purpose of the Study:
- To engineer a collagen hydrogel for controlled release of IFNA2b.
- To reduce IFNA2b diffusion and associated side effects.
- To evaluate the in vitro and in vivo antitumor activity of the engineered hydrogel.
Main Methods:
- Constructed a collagen hydrogel loaded with IFNA2b fused to a collagen-binding domain.
- Assessed the apoptotic activity of the fusion protein against MCF-7 cells in vitro.
- Evaluated the diffusion rate of the fusion protein from the collagen matrix.
- Tested the hydrogel's efficacy in a mouse xenograft tumor model.
Main Results:
- The IFNA2b fusion protein retained apoptotic activity in vitro.
- The fusion protein exhibited higher affinity for collagen type I, leading to slower diffusion.
- Collagen hydrogels with the fusion protein showed controlled release and in vitro apoptotic activity.
- In vivo studies demonstrated reduced tumor size and extended survival in mice.
Conclusions:
- Engineered collagen hydrogels provide a promising platform for controlled delivery of IFNA2b.
- This approach mitigates rapid diffusion and enhances therapeutic potential for cancer immunotherapy.
- The developed system shows moderate antitumor activity in vivo, warranting further investigation.
