Cancer immunotherapy has been intensively investigated in both preclinical and clinical studies.Whereas chemotherapies use cytotoxic drugs to kill tumor cells,cancer immunotherapy is based on the ability of the immune...Cancer immunotherapy has been intensively investigated in both preclinical and clinical studies.Whereas chemotherapies use cytotoxic drugs to kill tumor cells,cancer immunotherapy is based on the ability of the immune system to fight cancer.Tumors are intimately associated with the immune system:they can suppress the immune response and/or control immune cells to support tumor growth.Immunotherapy has yielded promising results in clinical practice,but some patients show limited responses.This may reflect the complexities of the relationship between a tumor and the immune system.In an effort to improve the current immunotherapies,researchers have exploited nanomaterials in creating new strategies to cure tumors via modulation of the immune system in tumor tissues.Although extensive studies have examined the use of immune checkpoint-based immunotherapy,rather less work has focused on manipulating the innate immune cells.This review examines the recent approaches and challenges in the use of nanomaterials to modulate innate immune cells.展开更多
Cell membranes have recently emerged as a new source of materials for molecular delivery systems.Cell membranes have been extruded or sonicated to make nanoscale vesicles.Unlike synthetic lipid or polymeric nanopartic...Cell membranes have recently emerged as a new source of materials for molecular delivery systems.Cell membranes have been extruded or sonicated to make nanoscale vesicles.Unlike synthetic lipid or polymeric nanoparticles,cell membrane-derived vesicles have a unique multicomponent feature,comprising lipids,proteins,and carbohydrates.Because cell membrane-derived vesicles contain the intrinsic functionalities and signaling networks of their parent cells,they can overcome various obstacles encountered in vivo.Moreover,the different natural combinations of membranes from various cell sources expand the range of cell membrane-derived vesicles,creating an entirely new category of drug-delivery systems.Cell membrane-derived vesicles can carry therapeutic agents within their interior or can coat the surfaces of drug-loaded core nanoparticles.Cell membranes typically come from single cell sources,including red blood cells,platelets,immune cells,stem cells,and cancer cells.However,recent studies have reported hybrid sources from two different types of cells.This review will summarize approaches for manufacturing cell membrane-derived vesicles and treatment applications of various types of cell membrane-derived drug-delivery systems,and discuss challenges and future directions.展开更多
Conjugation of antibodies to nanoparticles allows specific cancer targeting,but conventional conjugation methods generate heterogeneous conjugations that cannot guarantee the optimal orientation and functionality of t...Conjugation of antibodies to nanoparticles allows specific cancer targeting,but conventional conjugation methods generate heterogeneous conjugations that cannot guarantee the optimal orientation and functionality of the conjugated antibody.Here,a molecular engineering technique was used for sitespecific conjugation of antibodies to nanoparticles.We designed an anti-claudin 3(CLDN3)antibody containing a single cysteine residue,h4 G3 cys,then linked it to the maleimide group of lipid polydopamine hybrid nanoparticles(LPNs).Because of their negatively charged lipid coating,LPNs showed high colloidal stability and provided a functional surface for site-specific conjugation of h4 G3 cys.The activity of h4 G3 cys was tested by measuring the binding of h4 G3 cys-conjugated LPNs(C-LPNs)to CLDN3-positive tumor cells and assessing its subsequent photothermal effects.C-LPNsspecifically recognized CLDN3-overexpressing T47 D breast cancer cells but not CLDN3-negative Hs578 T breast cancer cells.High binding of C-LPNs to CLDN3-overexpressing T47 D cells resulted in significantly higher temperature generation upon NIR irradiation and potent anticancer photothermal efficacy.Consistent with this,intravenous injection of C-LPNsin a T47 D xenograft mouse model followed by NIR irradiation caused remarkable tumor ablation compared with other treatments through high temperature increases.Our results establish an accurate antibody-linking method and demonstrate the possibility of developing therapeutics using antibody-guided nanoparticles.展开更多
The safety of nanomaterials, a crucial consideration for clinical translation, is enhanced by using building blocks that are biologically nontoxic. Here, we used poly(γ-glutamic acid)(γ-PGA) and dopamine as building...The safety of nanomaterials, a crucial consideration for clinical translation, is enhanced by using building blocks that are biologically nontoxic. Here, we used poly(γ-glutamic acid)(γ-PGA) and dopamine as building blocks of polymeric nanomaterials for carrying hydrophobic anticancer drugs. The introduction of phenylalanine onto γ-PGA enabled the resulting amphiphilic derivative of γ-PGA acid to self-assemble in the presence of the anticancer drug paclitaxel(PTX) to form PTX-encapsulated micelles.The surfaces of PTX-loaded micelles were then coated with polymerized dopamine(PDA). The PDAcoated, amphiphilic γ-PGA-based micelles(AM) carrying PTX(PDA/AM/P) exerted near-infraredresponsive photothermal effects. Near-infrared irradiation of cancer cells treated with PDA/AM/P nanoparticles produced a greater anticancer effect than that observed in other treatment groups, indicating a synergistic effect. Intravenous administration of PDA/AM/P completely ablated tumors and prevented their recurrence. Notably, the in vivo safety profile of PDA/AM/P nanoparticles allowed PTX to be delivered at a 3.6-fold higher dose than was possible with PTX solubilized in surfactant, and circumvented the side effects of the surfactant. These results support the multifunctional potential of PDA/AM for the delivery of various hydrophobic drugs and imaging dyes for safe translation of nanomaterials into the clinic.展开更多
In immunotherapy,ex vivo stimulation of T cells requires significant resources and effort.Here,we report artificial dendritic cell-mimicking DNA microflowers(DM)for programming T cell stimulation in situ.To mimic dend...In immunotherapy,ex vivo stimulation of T cells requires significant resources and effort.Here,we report artificial dendritic cell-mimicking DNA microflowers(DM)for programming T cell stimulation in situ.To mimic dendritic cells,DNA-based artificial dendritic microflowers were constructed,surface-coated with polydopamine,and further modified with anti-CD3 and anti-CD28 antibodies to yield antibody-modified DM(DM-A).The porous structure of DM-A allowed entrapment of the T cell-stimulating cytokine,ineterleukin-2,yielding interleukin-2-loaded DM-A(DM-AI).For comparison,polystyrene microparticles coated with polydopamine and modified with anti-CD3 and anti-CD28 antibodies(PS-A)were used.Compared to PS-A,DM-AI showed significantly greater contact with T cell surfaces.DM-AI provided the highest ex vivo expansion of cytotoxic T cells.Local injection of DM-AI to tumor tissues induced the recruitment of T cells and expansion of cytotoxic T cells in tumor microenvironments.Unlike the other groups,model animals injected with DM-AI did not exhibit growth of primary tumors.Treatment of mice with DM-AI also protected against growth of a rechallenged distant tumor,and thus prevented tumor recurrence in this model.DM-AI has great potential for programmed stimulation of CD8+T cells.This concept could be broadly extended for the programming of specific T cell stimulation profiles.展开更多
基金funded by research grants from the Ministry of Science and Future Planning,Republic of Korea(NRF2018R1A2A1A05019203NRF-2018R1A5A2024425)the Korean Health Technology R&D Project(No.HI15C2842),Ministry of Health&Welfare,Republic of Korea。
文摘Cancer immunotherapy has been intensively investigated in both preclinical and clinical studies.Whereas chemotherapies use cytotoxic drugs to kill tumor cells,cancer immunotherapy is based on the ability of the immune system to fight cancer.Tumors are intimately associated with the immune system:they can suppress the immune response and/or control immune cells to support tumor growth.Immunotherapy has yielded promising results in clinical practice,but some patients show limited responses.This may reflect the complexities of the relationship between a tumor and the immune system.In an effort to improve the current immunotherapies,researchers have exploited nanomaterials in creating new strategies to cure tumors via modulation of the immune system in tumor tissues.Although extensive studies have examined the use of immune checkpoint-based immunotherapy,rather less work has focused on manipulating the innate immune cells.This review examines the recent approaches and challenges in the use of nanomaterials to modulate innate immune cells.
基金supported by grants from the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(NRF-2021R1A2B5B03002123,NRF-2018R1A5A2024425,Republic of Korea)the Korea Medical Device Development Fund grant funded by the Korea government(the Ministry of Science and ICT,the Ministry of Trade,Industry and Energy,the Ministry of Health&Welfare,the Ministry of Food and Drug Safety+1 种基金NTIS Number:9991007273,Republic of Korea)the Korean Health Technology R&D Project(No.HI18C2177,HI19C0664,Republic of Korea),Ministry of Health&Welfare
文摘Cell membranes have recently emerged as a new source of materials for molecular delivery systems.Cell membranes have been extruded or sonicated to make nanoscale vesicles.Unlike synthetic lipid or polymeric nanoparticles,cell membrane-derived vesicles have a unique multicomponent feature,comprising lipids,proteins,and carbohydrates.Because cell membrane-derived vesicles contain the intrinsic functionalities and signaling networks of their parent cells,they can overcome various obstacles encountered in vivo.Moreover,the different natural combinations of membranes from various cell sources expand the range of cell membrane-derived vesicles,creating an entirely new category of drug-delivery systems.Cell membrane-derived vesicles can carry therapeutic agents within their interior or can coat the surfaces of drug-loaded core nanoparticles.Cell membranes typically come from single cell sources,including red blood cells,platelets,immune cells,stem cells,and cancer cells.However,recent studies have reported hybrid sources from two different types of cells.This review will summarize approaches for manufacturing cell membrane-derived vesicles and treatment applications of various types of cell membrane-derived drug-delivery systems,and discuss challenges and future directions.
基金funded by grants from the Global Core Research Center(GCRC,Grant No.2011-0030001)of the National Research Foundation(NRF),Ministry of Science and ICT(MSIT),Republic of Koreathe MSIT,Republic of Korea(NRF-2018R1A2A1A05019203+1 种基金NRF-2018R1A5A2024425)the Korean Health Technology R&D Project(No.HI19C0664),Ministry of Health&Welfare,Republic of Korea
文摘Conjugation of antibodies to nanoparticles allows specific cancer targeting,but conventional conjugation methods generate heterogeneous conjugations that cannot guarantee the optimal orientation and functionality of the conjugated antibody.Here,a molecular engineering technique was used for sitespecific conjugation of antibodies to nanoparticles.We designed an anti-claudin 3(CLDN3)antibody containing a single cysteine residue,h4 G3 cys,then linked it to the maleimide group of lipid polydopamine hybrid nanoparticles(LPNs).Because of their negatively charged lipid coating,LPNs showed high colloidal stability and provided a functional surface for site-specific conjugation of h4 G3 cys.The activity of h4 G3 cys was tested by measuring the binding of h4 G3 cys-conjugated LPNs(C-LPNs)to CLDN3-positive tumor cells and assessing its subsequent photothermal effects.C-LPNsspecifically recognized CLDN3-overexpressing T47 D breast cancer cells but not CLDN3-negative Hs578 T breast cancer cells.High binding of C-LPNs to CLDN3-overexpressing T47 D cells resulted in significantly higher temperature generation upon NIR irradiation and potent anticancer photothermal efficacy.Consistent with this,intravenous injection of C-LPNsin a T47 D xenograft mouse model followed by NIR irradiation caused remarkable tumor ablation compared with other treatments through high temperature increases.Our results establish an accurate antibody-linking method and demonstrate the possibility of developing therapeutics using antibody-guided nanoparticles.
基金supported by grants from the Ministry of Science and ICT, Republic of Korea (NRF-2018R1A2A1A05019203 and NRF-2018R1A5A2024425)from the Korean Health Technology R&D Project (Nos. HI15C2842 and HI18C2177)Ministry of Health & Welfare, Republic of Korea
文摘The safety of nanomaterials, a crucial consideration for clinical translation, is enhanced by using building blocks that are biologically nontoxic. Here, we used poly(γ-glutamic acid)(γ-PGA) and dopamine as building blocks of polymeric nanomaterials for carrying hydrophobic anticancer drugs. The introduction of phenylalanine onto γ-PGA enabled the resulting amphiphilic derivative of γ-PGA acid to self-assemble in the presence of the anticancer drug paclitaxel(PTX) to form PTX-encapsulated micelles.The surfaces of PTX-loaded micelles were then coated with polymerized dopamine(PDA). The PDAcoated, amphiphilic γ-PGA-based micelles(AM) carrying PTX(PDA/AM/P) exerted near-infraredresponsive photothermal effects. Near-infrared irradiation of cancer cells treated with PDA/AM/P nanoparticles produced a greater anticancer effect than that observed in other treatment groups, indicating a synergistic effect. Intravenous administration of PDA/AM/P completely ablated tumors and prevented their recurrence. Notably, the in vivo safety profile of PDA/AM/P nanoparticles allowed PTX to be delivered at a 3.6-fold higher dose than was possible with PTX solubilized in surfactant, and circumvented the side effects of the surfactant. These results support the multifunctional potential of PDA/AM for the delivery of various hydrophobic drugs and imaging dyes for safe translation of nanomaterials into the clinic.
基金supported by grants from the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT,Republic of Korea(NRF-2021R1A2B5B03002123,NRF-2018R1A5A2024425),the Ministry of Education(NRF-2020R1I1A1A01070084,NRF-2020R1A6A3A01099750)the Korean Health Technology R&D Project(No.HI18C2177)Ministry of Health&Welfare,and a Korea Medical Device Development Fund grant funded by the Korean government(the Ministry of Science and ICT,the Ministry of Trade,Industry and Energy,the Ministry of Health&Welfare,the Ministry of Food and Drug Safety)(Project Number:9991007273,KMDF_PR_20200901_0106),Republic of Korea.
文摘In immunotherapy,ex vivo stimulation of T cells requires significant resources and effort.Here,we report artificial dendritic cell-mimicking DNA microflowers(DM)for programming T cell stimulation in situ.To mimic dendritic cells,DNA-based artificial dendritic microflowers were constructed,surface-coated with polydopamine,and further modified with anti-CD3 and anti-CD28 antibodies to yield antibody-modified DM(DM-A).The porous structure of DM-A allowed entrapment of the T cell-stimulating cytokine,ineterleukin-2,yielding interleukin-2-loaded DM-A(DM-AI).For comparison,polystyrene microparticles coated with polydopamine and modified with anti-CD3 and anti-CD28 antibodies(PS-A)were used.Compared to PS-A,DM-AI showed significantly greater contact with T cell surfaces.DM-AI provided the highest ex vivo expansion of cytotoxic T cells.Local injection of DM-AI to tumor tissues induced the recruitment of T cells and expansion of cytotoxic T cells in tumor microenvironments.Unlike the other groups,model animals injected with DM-AI did not exhibit growth of primary tumors.Treatment of mice with DM-AI also protected against growth of a rechallenged distant tumor,and thus prevented tumor recurrence in this model.DM-AI has great potential for programmed stimulation of CD8+T cells.This concept could be broadly extended for the programming of specific T cell stimulation profiles.
