Design And Anti-tumor Immunity Study Of Carrier Material-free Nanoassembly Based On Doxorubicin Prodrug And SiRNA

Doxorubicin(DOX)can elicit effective antitumor immunity responses by inducing immunogenic cell death(ICD)but also triggers upregulated expression of various immunosuppressive genes to counteract the ICD effect.To resolve this conflict,a carrier material-free nanoassembly based on acid-activatable DOX prodrug and small interfering RNA(siRNA)was developed to synergistically induce ICD and reverse immunosuppression.The carrier material-free nanoassembly with rather high drug contents(4.13% for siRNA and 21.67% for DOX)was formed via cooperative π-π stacking and electrostatic interactions.The formed nanoassembly,termed as PEG@D:siRNA,possessed a well-defined nanostructure: a core consisting of DOX plus siRNA and a shell consisting of polyethylene glycol(PEG).It has been demonstrated that this carrier material-free nanoassembly carrying siRNA targeting PD-L1 can significantly increase tumor-infiltrating T lymphocytes,improve interferon-γ(IFN-γ)expression,and ultimately strengthen the ICD effect of the DOX prodrug,resulting in a significantly enhanced anticancer immune response and superior tumor growth inhibition.In addition,carrier material-free nanoassembly PEG@D:siRNA can also be conveniently extended as a general strategy to combine chemotherapy and immunotherapy,providing a facile avenue for improving cancer chemoimmunotherapy.