Hybrid micelles codelivering shikonin and IDO-1 siRNA enhance immunotherapy by remodeling immunosuppressive tumor microenvironment.

Cancer immunotherapy is becoming an important option for malignant tumors treatment. Unfortunately, lacking intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and immunosuppressive tumor microenvironment (ITM) remian primary barriers that immensely hamper its further clinical application. For boosting immune response and rebuilding the ITM, valid hybrid micelles (SK/siIDO1-HMs) delivering shikonin (SK) and IDO-1 knockdown siRNA (siIDO1) were conducted. SK/siIDO1-HMs had sufficient circulation time, favorable intratumoral accumulation and rapidly release in the cytoplasm. Importantly, SK was demonstrated to significantly elicit intratumoral accumulation of CTLs through inducing immunogenic cell death (ICD) of tumor cells. Moreover, siIDO1 downregulated the IDO-1-caused immunosuppression and restrained regulatory T lymphocytes (Tregs). In summary, SK/siIDO1-HMs displayed a remarkable potential for tumor therapy via triggering the ICD and moderating the IDO-1-triggered immunosuppression.