Efficient in vivo delivery of immunomodulating biomolecules and enhanced antitumor immunity using multifunctional hybrid nanoconjugates (P4275)

Immunotherapy is regarded as a method of attractive treatment for cancer. Especially, dendritic cells (DCs) represent important targets for cell-mediated immunotherapy in cancer because they can capture tumor antigens that are released from tumor cells and migrate to the tumor-draining lymph nodes, where they present the antigens to T cells and secrete the pro-inflammatory cytokines that enhance T cell activation. However, immunosuppressive factors, such as signal transducer and activator of transcription-3 (STAT3), represent a major limitation for DCs-based cancer therapies. In this study, we have designed and synthesized an immunomodulatory hybrid nanoconjugates (HNC) system based on polymer nanocomposites containing quantum dots (QDs; as imaging tracers) that are decorated with CpG ODNs (as a TLR9 ligand) and STAT3 siRNAs (as an immunosuppressive gene silencer) for the efficient immunotherapeutic cancer therapy. These HNC efficiently targeted immune cells, induced TLR activation, and silenced immunosuppressive genes. Simultaneous in vivo delivery of STAT3 siRNA and CpG ODN to DCs in the tumor microenvironment induced both the inhibition of STAT3 and activation of DCs by CpG ODNs, and synergistically elicited anti-tumor effects. By using NIR-emitting QDs, the migration of in vivo DCs to lymph nodes was also tracked by real-time NIR fluorescence imaging. In the future, these studies are expected to facilitate the development of immune cell-based cancer therapy.