Carbon-dots-based Nanovaccines For Enhanced Cancer Immunotherapy

Cancer nanovaccines have attracted significant interest as a representative strategy for cancer immunotherapy.However,limited immunogenicity,inadequate antigen expression and low response rates limit their therapeutic applications.Because of their small size,biocompatibility,protein-like dimensions,abundant functional groups and nanoscale chirality,carbon dots(CDs)can not only carry and deliver antigens,but also induce cellular and humoral immune responses,and thus can be used as nanocarriers to improve the efficacy of cancer immunotherapy.In this thesis,we have investigated the synthesis of CDs-based nanovaccines and their application in cancer immunotherapy.The major content is as follows:(1)Chiral carbon dots(L/D-CDs)were prepared from citric acid(CA)and L/Dglutamic acid(L/D-Glu),and chiral nanovaccines(L/D-OVA)were fabricated using ovalbumin(OVA)as a model antigen.The L/D-OVA nanovaccine was effectively internalized by mouse bone marrow-derived dendritic cells(BMDCs),promoted BMDC maturation,effectively cross-presented to T cells,and inhibited the growth of B16-OVA melanoma.(2)CDs were prepared from glycerol(Gly)and polyethyleneimine(PEI),named GCDs.since the maleimide group in maleimide hexanoic acid can undergo Michael addition reaction and conjugate with antigens.Therefore,we grafted maleimidyl hexanoic acid onto the surface of GCDs to obtain GMal.tumor antigen-based nanovaccines(GMal+B16F10-Ag and GMal+CT26-Ag)were constructed by conjugating GMal with tumor cell-derived antigens(B16F10-Ag and CT26-Ag).Both nanovaccines could be efficiently taken up by dendritic cells(DC2.4),promoted DC cell maturation,cross-presented antigens to T cells,and were specific for B16F10 melanoma and CT26 colon cancer,and significantly inhibited tumor growth.This work illustrates the promise of CDs as multifunctional carriers to deliver antigens for optimal immunotherapeutic effects.