Self‐Immolated Nanoadjuvant for In Situ Vaccination Immunotherapy of Colorectal Cancer

Abstract

Vaccination immunotherapy has revolutionized cancer treatment modalities. Although the immunomodulatory adjuvant generally employs for potentiating vaccine response, systemic administration may drive immune‐related side effects, even immune tolerance. Therefore, tunable immunoadjuvants are highly desirable to simultaneously stimulate the immune response and mitigate systemic toxicity. Self‐immolated nanoadjuvants are herein reported to potentiate vaccination immunotherapy of cancer. The nanoadjuvants are engineered by co‐assembling an intracellular acidity‐ionizable polymeric agonist of toll‐like receptor 7/8 resiquimod (R848) and polymeric photosensitizer pyropheophorbide a (PPa). The resultant nanoadjuvants specifically accumulated at the tumor site via passive targeting and are dissociated in the acidic endosome versicles to activate PPa via protonation of the polymer backbone. Upon 671 nm laser irradiation, PPa performed photodynamic therapy to induce immunogenic cell death of tumor cells and subsequently released R848 in a customized manner, which synergistically activated dendritic cells (DCs), promoted antigen cross‐presentation, and eventually recruited cytotoxic T lymphocytes for tumor regression. Furthermore, the synergistic in situ vaccination immunotherapy with immune checkpoint blockade induce sustained immunological memory to suppress tumor recurrence in the rechallenged colorectal tumor model.

Self-Assembled R848/Chlorin e6 Nanoparticles for Combinatorial Immunotherapy of Head and Neck Squamous Cell Carcinoma

“…In this study, TME-regulated nanomedicine (termed as CR NPs) was engineered by the self-assembly of R848 and a photodynamic therapy (PDT) photosensitizer (chlorin e6, Ce6) for combinatorial immunotherapy. Compared to previous reports, this approach for developing NPs circumvented the issues of complex preparation, conjugating yield, and the formation of new compounds. , The assembled NPs efficiently accumulated in tumors, enhancing the bioavailability of R848 and reversing the immunosuppressive TME. In addition, loaded Ce6-induced photodynamic immunogenic cell death (ICD) and activated the stimulator of the interferon genes (STING) pathway in tumor cells, further amplifying antitumor immunity and inhibiting the growth of tumors (Scheme ).…”