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

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.