Nanotechnology For Anti-tumor Immunotherapy Via Dendritic Cells

Dendritic cells(DC)are the most important antigen presenting cells(APC).They play a central role in regulating immune tolerance and activation and determine the outcome of the immune response.Nanotechnology-based engineering of antigen and adjuvant can enhance the efficacy of antitumor immunity by altering their co-localization in DC,biodistribution,and release kinetics.Herein,the optimum antigen and adjuvant delivery offered by multi-functional hydrogel platform and self-assembled peptide-ligand nanoparticles to DC,which could awaken the innate immune and adaptive immune systems to inhibit the growth of malignancies.The antigen released from the scaffold-like structure in a sustained manner may be of interest for driving anti-tumor T-cell responses.However,the activation of immune cells is not high enough for valid cancer treatment.In the first part of this study,the injectable hydrogel is used to generate a local microenvironment,which co-localizes inflammatory cytokines,tumor antigen,and immune danger signals in situ.This strategy not only inhibited the tumor metastasis but also prolongs the survival time of mice bearing a tumor.The regulation of the immune cells by the construct a local immune microenvironment has great potential in cancer immunotherapy.Immature DC involved in silencing of T cell immune responses and susceptible to immune tolerance for cancer immunotherapy.The ligands of Toll-like receptors(TLR)induce maturation of DC.In the second part of this study,the antigen-ligand nanoparticle,assemble is driven by electrostatic and hydrophobic interaction,make the presentation and maturation occur in the same DC and activating innate and adaptive immunity.The antigen-ligands nanoparticle can trigger antitumor immunity response,inhibiting tumor growth and prolonging the survival time of the mice.Innate and adaptive immunity activated by antigen-ligand nanoparticles can improve the tumor treatment.In the third part of this study,more ligands and their combination are involved in the nano-vaccines assemble.The combination of TLR ligands can enhance the specific anti-tumor immune response,significantly inhibit the growth of melanoma and prostate cancer,some of the prostate cancer even completely disappeared,suggesting that the antigen-ligand nanoparticles have great potential in anti-tumor immunotherapy.