Boric acid functionalized carbon nanotheranostic platform for the hierarchical delivery of immune adjuvants and chemotherapy agents

Chemotherapy combined with immunotherapy represents a promising combination therapy for tumor treatment. The low targeting of chemotherapeutic drugs and the potential immune-related adverse events (irAEs) of immune adjuvants hinder the realization of combination therapy. To solve these problems, we propose to further conjugate immunoadjuvant OVA using boric acid (BA) modified drug-carrying carbon dots, and develop a multifunctional nano drug delivery system for hierarchical targeting of focal sites (RCD@DOX/BA-O). From a mechanistic perspective, based on the pKa of BA, RCD@DOX/BA can couple OVA (1, 3-n-diol) under alkaline conditions and release OVA under tumor microenvironment, which could prevent the occurrence of irAEs. Furthermore, the exposed BA was able to combine with sialic acid (SA) (1, 2-n-diol) under the acidic tumor microenvironment, thereby enhancing its tumor-targeting capabilities. Specially, the immune effect (tumor-associated macrophages (TAMs) to M1) of OVA and the tumor targeted enhancement was verified by cell experiments. The treatment effect of RCD@DOX/BA-O was further proved on animal level. Overall, our finding suggests that the synthesized RCD@DOX/BA-O enabling synergistic chemotherapy and immunotherapy through hierarchical targeting to enhance anti-tumor efficacy and reduce irAEs. It is of great significance for targeted immunotherapy and improving the therapeutic effect of tumor.