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.