Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin(DOX) and Toll-like receptor 7 agonist imiquimod...Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin(DOX) and Toll-like receptor 7 agonist imiquimod(IMQ) in low molecular weight heparin(LMWH)-D-α-tocopheryl succinate(TOS) micelles(LT). In this process, LMWH and TOS were conjugated by ester bond and they were not only served as the hydrophilic and hydrophobic segments of the carrier, but also exhibited strong anti-metastasis effect. The direct killing of tumor cells mediated by DOX-loaded micelles(LT-DOX)generated tumor-associated antigens, initiating tumor-specific immune responses in combination with IMQ-loaded micelles(LT-IMQ). Furthermore, the blockade of immune checkpoint with programmed cell death ligand 1(PD-L1) antibody further elevated the immune responses by up-regulating the maturation of DCs as well as the ratios of CD8+ CTLs/Treg and CD4+ Teff/Treg. Therefore, such a multifunctional strategy exhibited great potential for inhibiting the growth of orthotopic and metastatic breast cancer.展开更多
基金funded by the Major Projects of the National Natural Science Foundation of China(81690261)the National Natural Science Foundation of China(81703450)the Postdoctoral Research Foundation of China(2017M620429)
文摘Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin(DOX) and Toll-like receptor 7 agonist imiquimod(IMQ) in low molecular weight heparin(LMWH)-D-α-tocopheryl succinate(TOS) micelles(LT). In this process, LMWH and TOS were conjugated by ester bond and they were not only served as the hydrophilic and hydrophobic segments of the carrier, but also exhibited strong anti-metastasis effect. The direct killing of tumor cells mediated by DOX-loaded micelles(LT-DOX)generated tumor-associated antigens, initiating tumor-specific immune responses in combination with IMQ-loaded micelles(LT-IMQ). Furthermore, the blockade of immune checkpoint with programmed cell death ligand 1(PD-L1) antibody further elevated the immune responses by up-regulating the maturation of DCs as well as the ratios of CD8+ CTLs/Treg and CD4+ Teff/Treg. Therefore, such a multifunctional strategy exhibited great potential for inhibiting the growth of orthotopic and metastatic breast cancer.
