Injectable, Thixotropic, and Multi-Responsive Silk Fibroin Hydrogel for Localized and Synergistic Tumor Therapy

41 Pages Posted: 15 Aug 2019

See all articles by Shuangquan Gou

Shuangquan Gou

State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University

Dengchao Xie

Institute for Clean Energy and Advanced Materials, School of Materials and Energy, Southwest University

Ya Ma

Institute for Clean Energy and Advanced Materials, School of Materials and Energy, Southwest University

Yamei Huang

Institute for Clean Energy and Advanced Materials, School of Materials and Energy, Southwest University

Shiqin Deng

Institute for Clean Energy and Advanced Materials, School of Materials and Energy, Southwest University

Xiaoling Tong

State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University

Fangyin Dai

State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University; Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University

Chenhui Wang

Chongqing University - School of Pharmaceutical Sciences

Bo Xiao

State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University; Institute for Clean Energy and Advanced Materials, School of Materials and Energy, Southwest University; Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University

Date Written: August 12, 2019

Abstract

Combinational cancer therapy offers a promising strategy to overcome the limitations of single-drug treatment, including limited therapeutic efficacy, serious side effects, and low survival rate. Injectable silk fibroin (SF) hydrogel has emerged as an effective platform for localized treatment. Herein, hydrophilic SF (HSF) was extracted from regenerated SF and self-assembled into hydrogel within 2-6 h. The obtained HSF hydrogel showed obvious viscoelasticity, thixotropic behavior, and self-healing performance. Interestingly, this hydrogel also exhibited excellent stimuli-responsive drug release profiles when triggered by multiple factors (acidity, reactive oxygen species, glutathione, hyperthermia, and near infrared (NIR)), suggesting that it could achieve spatially and temporally on-demand drug release in response to tumor microenvironment and extra-tumor NIR irradiation. Importantly, intratumoral injection of doxorubicin (DOX)/Cy7-loaded HSF-based hydrogel (DOX/Cy7-hydrogel) plus NIR irradiation exerted the best anti-tumor effect among all the treatment groups, revealing the strong synergistic effects of chemo/photothermal/photodynamic therapy. It is worth noting that this DOX/Cy7-hydrogel could almost eliminate the entire tumor masses, significantly prolonging the survival time of tumor-bearing mice over 60 days without detectable adverse effects. Collectively, our findings suggest that this injectable DOX/Cy7-hydrogel with thixotropic and multi-stimuli responsive properties could be developed as a promising platform for localized and synergistic treatment of cancer.

Keywords: Injectability, Thixotropism, Multi-Responsibility, Silk Fibroin Hydrogel, Combination Therapy

Suggested Citation

Gou, Shuangquan and Xie, Dengchao and Ma, Ya and Huang, Yamei and Deng, Shiqin and Tong, Xiaoling and Dai, Fangyin and Wang, Chenhui and Xiao, Bo, Injectable, Thixotropic, and Multi-Responsive Silk Fibroin Hydrogel for Localized and Synergistic Tumor Therapy (August 12, 2019). Available at SSRN: https://ssrn.com/abstract=3435909 or http://dx.doi.org/10.2139/ssrn.3435909

Shuangquan Gou (Contact Author)

State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University

China

Dengchao Xie

Institute for Clean Energy and Advanced Materials, School of Materials and Energy, Southwest University

China

Ya Ma

Institute for Clean Energy and Advanced Materials, School of Materials and Energy, Southwest University

China

Yamei Huang

Institute for Clean Energy and Advanced Materials, School of Materials and Energy, Southwest University

China

Shiqin Deng

Institute for Clean Energy and Advanced Materials, School of Materials and Energy, Southwest University

China

Xiaoling Tong

State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University

China

Fangyin Dai

State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University ( email )

China

Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University ( email )

China

Chenhui Wang

Chongqing University - School of Pharmaceutical Sciences

China

Bo Xiao

State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University ( email )

China

Institute for Clean Energy and Advanced Materials, School of Materials and Energy, Southwest University ( email )

China

Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University ( email )

China

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