Mesoporous polydopamine Targeting CDK4/6 Inhibitor toward Brilliant Synergistic Immunotherapy of Breast Cancer

Abstract Immunotherapy utilizing anti‐PD‐L1 blockade has achieved dramatic success in clinical breast cancer management but is often hampered by the limited immune response. Increasing evidence shows that immunogenic cell death (ICD) recently arises as a promising strategy for enlarging tumor immunogenicity and eliciting systemic anti‐tumor immunity effectively. However, developing simple but versatile, highly efficient but low‐toxic, biosafe, and clinically available transformed ICD inducers remains a huge demand and is highly desirable. Herein, a multifunctional ICD inducer is purposefully developed A6‐MPDA@PAL by integrating photothermal therapy (PTT) nanoplatforms mesoporous polydopamine (MPDA), CDK4/6 inhibitor palbociclib (PAL), and CD44‐specific targeting A6 peptide in a simple way for augmenting the immune antitumor efficacy of anti‐PD‐L1 therapy. Remarkably, the light‐inducible nanoplatforms exhibit multiple favorable therapeutic features ensuring a superior and biosafe PTT/chemotherapy efficacy. Together with stronger accumulative ICD induction, single administration of A6‐MPDA@PAL can trigger robust systemic antitumor immunity and abscopal effect with the assistance of anti‐PD‐L1 blockade by fascinating the intratumoral infiltration of T lymphocytes and reversing the immunosuppressive tumor microenvironment simultaneously, therapy achieving brilliant synergistic immunotherapy with effective tumor ablation. This study presents a simple and smart ICD inducer opening up attractive clinical possibilities for reinforcing the anti‐PD‐L1 therapy against breast cancer.