期刊
ADVANCED MATERIALS
卷 33, 期 16, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202008518
关键词
cancer theranostics; EphA2 receptors; immunologically cold; hot tumors; molecule‐ targeted anticancer agents; supramolecular self‐ assembling peptides
类别
资金
- NSFC [51961160730, 51873092, 81921004]
- National Key R&D Program of China (Intergovernmental Cooperation Project) [2017YFE0132200]
- Tianjin Science Fund for Distinguished Young Scholars [19JCJQJC61200]
Supramolecular self-assembling peptide systems have shown great potential for cancer theranostics, with the ability to target specific receptors and promote antitumor responses. The designed peptide agent can visualize and suppress cancer cell proliferation by targeting EphA2 receptors, and also convert immunologically cold tumors to hot by inducing immunogenic cell death and recruiting tumor-infiltrating T cells. This study introduces a new category of agents capable of converting cold to hot tumors through supramolecular self-assembly.
Supramolecular self-assembling peptide systems are attracting increasing interest in the field of cancer theranostics. Additionally, transformation of the immunologically cold tumor microenvironment into hot is of great importance for obtaining high antitumor responses for most immunotherapies. However, as far as it is known, there are nearly no studies on self-assembling peptides reported to be able to convert cold to hot tumors. Herein, a self-assembling peptide-based cancer theranostic agent (named DBT-2FFGYSA) is designed and synthesized, which can target tumor-specific transmembrane Eph receptor A2 (EphA2) receptors selectively and make the receptors form large aggregates. Such aggregate formation promotes the cross-phosphorylations among EphA2 receptors, leading to signal transduction of antitumor pathway. As a consequence, DBT-2FFGYSA can not only visualize EphA2 receptors in a fluorescence turn-on manner, but also specifically suppress the EphA2 receptor-overexpressed cancer cell proliferation and tumor growth. What is more, DBT-2FFGYSA also serves as an effective agent to convert immunologically cold tumors to hot by inducing the immunogenic cell death of EphA2 receptor-overexpressed cancer cells and recruiting massive tumor-infiltrating T cells. This study, thus, introduces a new category of agents capable of converting cold to hot tumors by pure supramolecular self-assembly without any aid of known anticancer drugs.
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