Scheme 1.

a) Schematic illustration of the HCJSP prodrug nanoparticle prepared via the host–guest interaction between HA‐CD and AD‐SS‐JQ1 and AD‐SS‐PPa. b) Proposed mechanisms of HCJSP‐based combinatory immunotherapy of pancreatic tumor by eliciting immunogenicity and overcoming adaptive immune resistance. HCJSP‐mediated PDT initiates ICD of the tumor cells, promotes DC maturation, and activates the CTLs for tumor regression. Meanwhile, BRD4i JQ1 can relieve PDT‐promoted glycolysis and immunosuppresive tumor microenvironment by impeding the transcription of c‐Myc and the downstream genes of the c‐Myc pathway, including HK‐2 and LDHA. Meanwhile, JQ1 can specifically downregulate IFN‐γ‐inducible PD‐L1 expression on the surface of the tumor cells for combating PDT‐inducible adaptive immune evasion.