Herein,we report on a tumor nanovaccine LMNP@CM that enhances the process of antigen-presenting by stimulating the immune system to uptake tumor antigens actively.The nanovaccine is comprised of polyethylene glycol mo...Herein,we report on a tumor nanovaccine LMNP@CM that enhances the process of antigen-presenting by stimulating the immune system to uptake tumor antigens actively.The nanovaccine is comprised of polyethylene glycol modified liquid metal nanoparticles(LMNP)and tumor cell membra nes(CM)as antigens.Under 808 nm irradiation,the photothermal con version effect of injected LMNP can cause mild local inflammation,and subsequently induces antigen-presenting cells active recruitment and facilitates cellular uptake of tumor antigens.Meanwhile,because of the immune adjuvant effect of metal materials,the nanovaccine LMNP@CM promotes the maturation and activation of antigen-presenting cells and induces anti-tumor immune response effectively.By priming the host immune recognition of tumor antigens,this nanovaccine displays prophylactic effects and significantly suppresses tumor growth in a mouse breast tumor model.The nanovaccine LMNP@CM represents a novel strategy of utilizing light-controlled means to actively induce anti-tumor immune processes,showing advanced therapeutic potentials and robust adaptability for treating multiple tumors by changing the loaded antigens.展开更多
T regulatory(Treg) cell is a major immunosuppressive factor that restrains the antitumor effect of immunotherapy, because it gets more after the immune activation and is hardly to be eliminated. Here, an acid-sensitiv...T regulatory(Treg) cell is a major immunosuppressive factor that restrains the antitumor effect of immunotherapy, because it gets more after the immune activation and is hardly to be eliminated. Here, an acid-sensitive integrated nanodrug system is designed to activate antitumor immune response as well as locally deplete Treg cells with low side effect. The nanosystem is synthetized by coordinating doxorubicin(DOX) and pentoxifylline(PTX) with Zn ions, then stabilized via liposome encapsulation(denoted as DTX@Lipo). DTX@Lipo can activate antitumor immune effect by chemotherapy of DOX. Besides, the release of PTX inhibits c-Rel expression, leading to the reduction of Treg cells in tumor site. Owing to the good tumor accumulation and local drug release ability, DTX@Lipo exhibits better biosafety and convenience than traditional antibody blockade method for Treg cells depletion. According to the results of in vivo experiments, the nanodrug system can significantly increase the ratio between effector T(Teff) cells and Treg cells locally, resulting in an immunoactivated tumor microenvironment. Importantly, it exhibits significant antitumor effect when combined with PD-1 blockade therapy, providing great potential for tumor therapy.展开更多
基金supported by the National Natural Science Foundation of China(52073219 and 51833007)the National Key Research and Development Program of China(2019YFA0905603)。
基金financially supported by the National Natural Science Foundation of China(Nos.51833007,21721005 and 51690152).
文摘Herein,we report on a tumor nanovaccine LMNP@CM that enhances the process of antigen-presenting by stimulating the immune system to uptake tumor antigens actively.The nanovaccine is comprised of polyethylene glycol modified liquid metal nanoparticles(LMNP)and tumor cell membra nes(CM)as antigens.Under 808 nm irradiation,the photothermal con version effect of injected LMNP can cause mild local inflammation,and subsequently induces antigen-presenting cells active recruitment and facilitates cellular uptake of tumor antigens.Meanwhile,because of the immune adjuvant effect of metal materials,the nanovaccine LMNP@CM promotes the maturation and activation of antigen-presenting cells and induces anti-tumor immune response effectively.By priming the host immune recognition of tumor antigens,this nanovaccine displays prophylactic effects and significantly suppresses tumor growth in a mouse breast tumor model.The nanovaccine LMNP@CM represents a novel strategy of utilizing light-controlled means to actively induce anti-tumor immune processes,showing advanced therapeutic potentials and robust adaptability for treating multiple tumors by changing the loaded antigens.
基金supported by the National Natural Science Foundation of China(51833007,51703168,51690152,21674084)
文摘T regulatory(Treg) cell is a major immunosuppressive factor that restrains the antitumor effect of immunotherapy, because it gets more after the immune activation and is hardly to be eliminated. Here, an acid-sensitive integrated nanodrug system is designed to activate antitumor immune response as well as locally deplete Treg cells with low side effect. The nanosystem is synthetized by coordinating doxorubicin(DOX) and pentoxifylline(PTX) with Zn ions, then stabilized via liposome encapsulation(denoted as DTX@Lipo). DTX@Lipo can activate antitumor immune effect by chemotherapy of DOX. Besides, the release of PTX inhibits c-Rel expression, leading to the reduction of Treg cells in tumor site. Owing to the good tumor accumulation and local drug release ability, DTX@Lipo exhibits better biosafety and convenience than traditional antibody blockade method for Treg cells depletion. According to the results of in vivo experiments, the nanodrug system can significantly increase the ratio between effector T(Teff) cells and Treg cells locally, resulting in an immunoactivated tumor microenvironment. Importantly, it exhibits significant antitumor effect when combined with PD-1 blockade therapy, providing great potential for tumor therapy.
