Synthetic High-Density Lipoprotein-Based Nanomedicine to Silence SOCS1 in Tumor Microenvironment and Trigger Antitumor Immunity against Glioma

Immunotherapies have shed light on the treatment of many cancers, but have not improved the outcomes of glioma (GBM). Here, we demonstrated that suppressor of cytokine signaling 1 (SOCS1) was associated with the GBM-associated immunosuppression and developed a multifunctional nanomedicine, which silenced SOCS1 in the tumor microenvironment (TME) of GBM and triggered strong antitumor immunity against GBM. Synthetic high-density lipoprotein (sHDL) was selected as the nanocarrier and a peptide was used to facilitate the blood-brain-barrier (BBB) penetration. The nanocarrier was loaded with a small interfering RNA (siRNA), a peptide, and an adjuvant to trigger antitumor immunity. The nanomedicine concentrated on the TME in vivo, further promoting dendritic cell maturation and T cell proliferation, triggering strong cytotoxic T lymphocyte responses, and inhibiting tumor growth. Our work provides an alternative strategy to simultaneously target and modulate the TME in GBM patients and points to an avenue for enhancing the efficacy of immunotherapeutics. A nanomedicine was designed to modulate the tumor microenvironment (TME) against glioma (GBM). Upon intravenous injection, the nanomedicine penetrated the blood-brain barrier and accumulated within the TME of GBM-bearing mice, which subsequently abolished the negative feedback regulation function of SOCS1 on dendritic cell maturation and T cell proliferation, elicited strong cytotoxic T lymphocyte responses, and inhibited tumor growth.+image

Automated summary

This study demonstrates the potential of enhancing the efficacy of immunotherapy for glioma by targeting and modulating the tumor microenvironment. The researchers designed a nanomedicine that silenced SOCS1 and triggered a strong antitumor immune response, inhibiting tumor growth.