CXC Chemokine Receptor Type 4 Antagonistic Gold Nanorods Induce Specific Immune Responses and Long-Term Immune Memory to Combat Triple-Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is highly challenging in its treatment because of the lack of the targeted markers. TNBC patients are not able to acquire benefits from endocrine therapy and targeted therapy except for chemotherapy. CXCR4 is highly expressed on TNBC cells that mediated the tumor cell metastasis as well as proliferation by the response of its ligand CXCL12, therefore holding promising potential of a candidate target for the treatment. In this work, a novel conjugate of CXCR4 antagonist peptide E5 and gold nanorods was fabricated (AuNRs-E5), which was applied to murine breast cancer tumor cells and an animal model, aiming to induce endoplasmic reticulum stress by endoplasmic reticulum-targeted photothermal immunological effects. Results showed that AuNRs-E5 could induce much more generation of damage-related molecular patterns in 4T1 cells under laser irradiation than AuNRs, which significantly promoted the maturation of dendritic cells and stimulated systematic anti-tumor immune responses by enhancing the infiltration of CD8+T cells into the tumor and tumor-draining lymph node, downregulating the regulatory T lymphocytes, and upregulating M1 macrophages in tumors, reversing the microenvironment from “cold” tumors to “hot” tumors. The administration of AuNRs-E5 with laser irradiation not only inhibited the tumor growth significantly but also exerted specific long immune responses to the triple-negative breast cancer tumor cells, which led to the prolonged survival of the mice and the specific immunological memory.