The adhesive interaction between tumor cells and host cells or the extra cellular matrix plays a crucial role in metastasis. Due to the anti-metastasis effects of RGD (arginyl-glycyl -aspartic acid) and some oligosac...The adhesive interaction between tumor cells and host cells or the extra cellular matrix plays a crucial role in metastasis. Due to the anti-metastasis effects of RGD (arginyl-glycyl -aspartic acid) and some oligosaccharides, RGD-aPEG-Lactoside was prepared which will be used on anti-metastasis.展开更多
Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly kill...Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor cells.However,the insufficient oxygen delivery to deep tumor and the confronting Warburg effect"compromise the efficacy of hypoxia alleviation.Herein,we construct a cascade enzyme-powered nanomotor(NM-si),which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy.Catalase(Cat)and glucose oxidase(GOx)are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor(NM),with hexokinase-2(HK-2)siRNA further condensed(NM-si).The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H_(2)O_(2) gradient towards deep tumor,with hypoxia successfully alleviated in the meantime.The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis.In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME reconstruction.This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.展开更多
Platinum-based chemotherapy is used for non-small cell lung cancer(NSCLC).However,it has side effects and minimum efficacy against lung cancer metastasis.In this study,platinum-curcumin complexes were loaded into pH a...Platinum-based chemotherapy is used for non-small cell lung cancer(NSCLC).However,it has side effects and minimum efficacy against lung cancer metastasis.In this study,platinum-curcumin complexes were loaded into pH and redox dual-responsive nanoparticles(denoted as Pt-CUR@PSPPN)to facilitate intracellular release and synergistic anti-cancer effects.Pt-CUR@PSPPN was prepared by a nano-precipitation method and had a diameter of^100 nm.The nanoparticles showed increased anticancer effects both in vivo and in vitro.In addition,Pt-CUR@PSPPN blocked PI3K/AKT signal transduction pathway and inhibited MMP2 and VEGFR2,resulting in enhanced anti-metastatic activity.Furthermore,reduced side effects were also observed.In conclusion,Pt-CUR@PSPPN provided a novel and attractive therapeutic strategy for NSCLC.展开更多
Since the beginning of 2017,Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology,which sparkle diverse thoughts,interesting communications,and potential coll...Since the beginning of 2017,Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology,which sparkle diverse thoughts,interesting communications,and potential collaborations among researchers all over the world.In this article,10 more questions are presented as followed.Question 40.Why do mice being used as tumorigenesis models raised in different places or different conditions possess different tumor formation rate? Question 41.How could we generate more effective anti-metastasis drugs? Question 42.What is the molecular mechanism underlying heterogeneity of cancer cachexia in patients with the same pathologic type? Question 43.Will patients with oligo-metastatic disease be curable by immunotherapy plus stereotactic body radiotherapy? Question 44.Can the Warburg effect regulation be targeted for cancer treatment? Question 45.Why do adenocarcinomas seldom occur in the small intestine? Question 46.Is Epstein-Barr virus infection a causal factor for nasal natural killer/T cell lymphoma formation? Question 47.Why will not all but very few human papillomavirusinfected patients eventually develop cervical cancer? Question 48.Why do cervical carcinomas induced by human papilloma virus have a low mutation rate in tumor suppressor genes? Question 49.Can viral infection trigger lung cancer relapse?展开更多
We investigated the effect of a nicotine-and tar-free cigarette smoke extract (CSE) using an experimental metastasis mouse model which was intravenously injected with B16-BL6 mouse melanoma cells. Three-hour pretreatm...We investigated the effect of a nicotine-and tar-free cigarette smoke extract (CSE) using an experimental metastasis mouse model which was intravenously injected with B16-BL6 mouse melanoma cells. Three-hour pretreatment of cells with various concentrations of CSE (0, 0.1, 0.3, and 1%) dose-dependently reduced the number of lung metastatic nodules 14 days after tumor injection. To elucidate the mechanism of this anti-metastatic effect of CSE, we examined the invasion and migration activities of B16-BL6 cells pretreated with CSE for three hours in vitro. CSE significantly reduced the invasion of cells at 1% and the migration at 0.3% and 1%. Under the same pretreatment conditions, CSE had no effect on the proliferation of cells. These findings suggest that CSE contains some ingredients that suppress hematogenic lung metastasis via inhibition of the invasion and migration activities of mouse melanoma cells.展开更多
Background:Esophageal carcinoma is one of the most common malignant tumors worldwide,with China the hardest hit area accounts for nearly 50 percent of the morbidity and mortality each year.Despite the deepening of the...Background:Esophageal carcinoma is one of the most common malignant tumors worldwide,with China the hardest hit area accounts for nearly 50 percent of the morbidity and mortality each year.Despite the deepening of the research and treatment of esophageal carcinoma,its five-year survival rate is still less than 20%,partly because of the formation of drug resistance and after-effects with conventional treatment.Recent years,accumulating evidence suggests that natural medicines have remarkable effects on the aspect of anticancer without or with mild side effects,therefore,the anticancer drugs development on esophageal carcinoma has transitioned from chemical synthesis to natural medicines.China has the tradition of using Chinese herbal medicines for various diseases curing for thousands of years and has been proved to be effective,including esophageal carcinoma.With almost 10,000 Chinese herbal medicines have been excavated,the studies on Chinese herbal medicines for esophageal carcinoma is growing increasingly.Every Chinese herbal medicine is comprised of kinds of chemical compositions,exerts anticancer effect by targeting multiple targets via multiple signaling pathways with lower incidence rate of drug resistance and almost no side effects,which has caught increasingly attention.In this review,we summarized some monomers,extracts and composite of CHMs with anticancer activity on esophageal carcinoma by inhibiting proliferation,anti-metastasis,et al.,and elaborate their mechanisms of action,hoping this will be valuable for esophageal carcinoma treatment and drug development.展开更多
Mornaphthoate E(MPE)is a prenylated naphthoic acid methyl ester isolated from the roots of a famous Chinese medicinal plant Morinda officinalis and shows remarkable cytotoxicity against several human tumor cell lines....Mornaphthoate E(MPE)is a prenylated naphthoic acid methyl ester isolated from the roots of a famous Chinese medicinal plant Morinda officinalis and shows remarkable cytotoxicity against several human tumor cell lines.In the current project,the first total synthesis of(±)-MPE was achieved in seven steps and 5.6%overall yield.Then the in vitro anti-tumor activity of MPE was first assessed for both enantiomers in two breast cancer cells,with the levoisomer exerting slightly better potency.The in vivo anti-tumor effect was further verified by applying the racemate in an orthotopic autograft mouse model.Notably,MPE exerted promising anti-metastasis activity both in vitro and in vivo and showed no obvious toxicity on mice at the therapeutic dosage.Mechanistic investigations demonstrated that MPE acted as a tubulin polymerization stabilizer and disturbed the dynamic equilibrium of microtubules via regulating PI3K/Akt signaling.In conclusion,our work has provided a new chemical template for the future design and development of next-generation tubulin-targeting chemotherapies.展开更多
The application of photothermal therapy(PTT)is greatly limited by the low accumulation of photothermal agents,uneven photothermal distribution,and heat endurance of cancer cells.Worse still,despite PTT enhances immuno...The application of photothermal therapy(PTT)is greatly limited by the low accumulation of photothermal agents,uneven photothermal distribution,and heat endurance of cancer cells.Worse still,despite PTT enhances immunogenicity,the anti-tumor immune efficacy is still unsatisfactory due to the inefficient immunogenic cell death(ICD)induction and poor infiltration of immune cells.To solve the above problems of PTT,we developed hyaluronic acid(HA)modified hollow copper sulfide nanoparticles encapsulating diethyldithiocarbamate(DDTC)to construct a breast tumor targeting and near infrared(NIR)photo-responsive drug delivery system(D-HCuS@HA),which further combined with losartan to improve the accumulation and penetration in the tumor site.Upon irradiation,D-HCuS@HA realized enhanced PTT and released cytotoxic Cu(DDTC)_(2)to eliminate heat endurance tumor cells,thereby enhancing antitumor effect and inducing effective ICD.Moreover,the combination with losartan could remodel the tumor microenvironment,allowing more T cells to infiltrate into the tumor,and significantly inhibiting the occurrence and development of metastatic tumors.In vitro/vivo results revealed the great potential of D-HCuS@HA combined with losartan,which provides a new paradigm for anti-tumor and anti-metastases.展开更多
Objective：To investigate the antiproliferative and anti-metastasis effect of Xihuang Pill（西黄丸,XP） on human colorectal cancer cell and to explore the molecular mechanism by which it produces the effects.Methods：...Objective：To investigate the antiproliferative and anti-metastasis effect of Xihuang Pill（西黄丸,XP） on human colorectal cancer cell and to explore the molecular mechanism by which it produces the effects.Methods：Highly metastatic human colorectal cancer cell line LoVo was treated with low-,medium-,and highdose XP-containing serum（XP-L,XP-M,XP-H） groups for 48 h,cells intervened with no drug rat serum and PD98059[extracellular signal-regulated kinase（ERK） inhibitor]as negative and positive controls（NC and PC）groups.Cell proliferation assay was made using cell counting kit-8（CCK8）.The 8 μm pore-size transwell chamber and 4＇,6-diamidino-2-phenylindole（DAPI） staining were applied to examine the ability of invasion and migration of the cells.The protein expression of ERK1/2,zinc finger E-box-binding homeobox 1（ZEB1）,Scrib and lethal giant larvae homolog 2（Lgl2） was detected by Western blotting while the relative mRNA quantity of E-cadherin,N-cadherin,Occludin and junctional adhesion molecule-1（JAM1） was measured by realtime fluorescent quantitative polymerase chain reaction（RT-qPCR）.Results：XP induced a dose-dependent suppression on the proliferation of LoVo cells（P〈0.05 or P〈0.01）,with the inhibition rates varied from 27.30%to31.08%.Transwell assay showed that when preprocessed with PD98059 and XP-containing serum,the number of cells that passed the filter decreased significantly compared with that of NC group（P〈0.05 or P〈0.01）.Moreover,XP inhibited the protein expression of ERK1/2 and ZEB1（P〈0.05）;and up-regulated the protein expression of Scrib and Lgl2（P〈0.05）.The mRNA levels of E-cadherin,Occludin and JAM1 of the XP intervened groups and PC group markedly ascended（P〈0.05） while that of N-cadherin showed a descending tendency（P〉0.05）.Conclusion：XP intervention suppressed the ability of proliferation,invasion and migration of the LoVo cells.Regulating ZEB1-SCRIB Loop so as to recover epithelial phenotype and apical junctional complex might be one of the mechanisms by which XP produces the anti-metastasis effect.展开更多
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
文摘The adhesive interaction between tumor cells and host cells or the extra cellular matrix plays a crucial role in metastasis. Due to the anti-metastasis effects of RGD (arginyl-glycyl -aspartic acid) and some oligosaccharides, RGD-aPEG-Lactoside was prepared which will be used on anti-metastasis.
基金supported by National Natural Science Foundation of China(No.81961138009)the Fundamental Research Funds for the Central Universities(Nos.SCU2017A001,2018SCUH0024,China)+1 种基金111 Project(No.B18035,China)the Key Research and Development Program of Science and Technology Department of Sichuan Province(No.2020YFS0570,China)
文摘Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor cells.However,the insufficient oxygen delivery to deep tumor and the confronting Warburg effect"compromise the efficacy of hypoxia alleviation.Herein,we construct a cascade enzyme-powered nanomotor(NM-si),which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy.Catalase(Cat)and glucose oxidase(GOx)are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor(NM),with hexokinase-2(HK-2)siRNA further condensed(NM-si).The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H_(2)O_(2) gradient towards deep tumor,with hypoxia successfully alleviated in the meantime.The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis.In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME reconstruction.This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.
基金supported by the Programs of the National Natural Science Foundation of China(Grant Nos.81673368,81603046,81703446 and 81973257)
文摘Platinum-based chemotherapy is used for non-small cell lung cancer(NSCLC).However,it has side effects and minimum efficacy against lung cancer metastasis.In this study,platinum-curcumin complexes were loaded into pH and redox dual-responsive nanoparticles(denoted as Pt-CUR@PSPPN)to facilitate intracellular release and synergistic anti-cancer effects.Pt-CUR@PSPPN was prepared by a nano-precipitation method and had a diameter of^100 nm.The nanoparticles showed increased anticancer effects both in vivo and in vitro.In addition,Pt-CUR@PSPPN blocked PI3K/AKT signal transduction pathway and inhibited MMP2 and VEGFR2,resulting in enhanced anti-metastatic activity.Furthermore,reduced side effects were also observed.In conclusion,Pt-CUR@PSPPN provided a novel and attractive therapeutic strategy for NSCLC.
文摘Since the beginning of 2017,Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology,which sparkle diverse thoughts,interesting communications,and potential collaborations among researchers all over the world.In this article,10 more questions are presented as followed.Question 40.Why do mice being used as tumorigenesis models raised in different places or different conditions possess different tumor formation rate? Question 41.How could we generate more effective anti-metastasis drugs? Question 42.What is the molecular mechanism underlying heterogeneity of cancer cachexia in patients with the same pathologic type? Question 43.Will patients with oligo-metastatic disease be curable by immunotherapy plus stereotactic body radiotherapy? Question 44.Can the Warburg effect regulation be targeted for cancer treatment? Question 45.Why do adenocarcinomas seldom occur in the small intestine? Question 46.Is Epstein-Barr virus infection a causal factor for nasal natural killer/T cell lymphoma formation? Question 47.Why will not all but very few human papillomavirusinfected patients eventually develop cervical cancer? Question 48.Why do cervical carcinomas induced by human papilloma virus have a low mutation rate in tumor suppressor genes? Question 49.Can viral infection trigger lung cancer relapse?
文摘We investigated the effect of a nicotine-and tar-free cigarette smoke extract (CSE) using an experimental metastasis mouse model which was intravenously injected with B16-BL6 mouse melanoma cells. Three-hour pretreatment of cells with various concentrations of CSE (0, 0.1, 0.3, and 1%) dose-dependently reduced the number of lung metastatic nodules 14 days after tumor injection. To elucidate the mechanism of this anti-metastatic effect of CSE, we examined the invasion and migration activities of B16-BL6 cells pretreated with CSE for three hours in vitro. CSE significantly reduced the invasion of cells at 1% and the migration at 0.3% and 1%. Under the same pretreatment conditions, CSE had no effect on the proliferation of cells. These findings suggest that CSE contains some ingredients that suppress hematogenic lung metastasis via inhibition of the invasion and migration activities of mouse melanoma cells.
文摘Background:Esophageal carcinoma is one of the most common malignant tumors worldwide,with China the hardest hit area accounts for nearly 50 percent of the morbidity and mortality each year.Despite the deepening of the research and treatment of esophageal carcinoma,its five-year survival rate is still less than 20%,partly because of the formation of drug resistance and after-effects with conventional treatment.Recent years,accumulating evidence suggests that natural medicines have remarkable effects on the aspect of anticancer without or with mild side effects,therefore,the anticancer drugs development on esophageal carcinoma has transitioned from chemical synthesis to natural medicines.China has the tradition of using Chinese herbal medicines for various diseases curing for thousands of years and has been proved to be effective,including esophageal carcinoma.With almost 10,000 Chinese herbal medicines have been excavated,the studies on Chinese herbal medicines for esophageal carcinoma is growing increasingly.Every Chinese herbal medicine is comprised of kinds of chemical compositions,exerts anticancer effect by targeting multiple targets via multiple signaling pathways with lower incidence rate of drug resistance and almost no side effects,which has caught increasingly attention.In this review,we summarized some monomers,extracts and composite of CHMs with anticancer activity on esophageal carcinoma by inhibiting proliferation,anti-metastasis,et al.,and elaborate their mechanisms of action,hoping this will be valuable for esophageal carcinoma treatment and drug development.
基金This project was financially supported by the National Natural Science Foundation of China(No.82073729,22225105).
文摘Mornaphthoate E(MPE)is a prenylated naphthoic acid methyl ester isolated from the roots of a famous Chinese medicinal plant Morinda officinalis and shows remarkable cytotoxicity against several human tumor cell lines.In the current project,the first total synthesis of(±)-MPE was achieved in seven steps and 5.6%overall yield.Then the in vitro anti-tumor activity of MPE was first assessed for both enantiomers in two breast cancer cells,with the levoisomer exerting slightly better potency.The in vivo anti-tumor effect was further verified by applying the racemate in an orthotopic autograft mouse model.Notably,MPE exerted promising anti-metastasis activity both in vitro and in vivo and showed no obvious toxicity on mice at the therapeutic dosage.Mechanistic investigations demonstrated that MPE acted as a tubulin polymerization stabilizer and disturbed the dynamic equilibrium of microtubules via regulating PI3K/Akt signaling.In conclusion,our work has provided a new chemical template for the future design and development of next-generation tubulin-targeting chemotherapies.
基金supported by National Natural Science Foundation of China(No.82173762)Research Funds of Sichuan Science and Technology Department(Nos.2022JDJQ0050,2022YFS0334)111 Project(No.B18035)。
文摘The application of photothermal therapy(PTT)is greatly limited by the low accumulation of photothermal agents,uneven photothermal distribution,and heat endurance of cancer cells.Worse still,despite PTT enhances immunogenicity,the anti-tumor immune efficacy is still unsatisfactory due to the inefficient immunogenic cell death(ICD)induction and poor infiltration of immune cells.To solve the above problems of PTT,we developed hyaluronic acid(HA)modified hollow copper sulfide nanoparticles encapsulating diethyldithiocarbamate(DDTC)to construct a breast tumor targeting and near infrared(NIR)photo-responsive drug delivery system(D-HCuS@HA),which further combined with losartan to improve the accumulation and penetration in the tumor site.Upon irradiation,D-HCuS@HA realized enhanced PTT and released cytotoxic Cu(DDTC)_(2)to eliminate heat endurance tumor cells,thereby enhancing antitumor effect and inducing effective ICD.Moreover,the combination with losartan could remodel the tumor microenvironment,allowing more T cells to infiltrate into the tumor,and significantly inhibiting the occurrence and development of metastatic tumors.In vitro/vivo results revealed the great potential of D-HCuS@HA combined with losartan,which provides a new paradigm for anti-tumor and anti-metastases.
基金Supported by the National Natural Science Foundation of China(No.81273636)
文摘Objective：To investigate the antiproliferative and anti-metastasis effect of Xihuang Pill（西黄丸,XP） on human colorectal cancer cell and to explore the molecular mechanism by which it produces the effects.Methods：Highly metastatic human colorectal cancer cell line LoVo was treated with low-,medium-,and highdose XP-containing serum（XP-L,XP-M,XP-H） groups for 48 h,cells intervened with no drug rat serum and PD98059[extracellular signal-regulated kinase（ERK） inhibitor]as negative and positive controls（NC and PC）groups.Cell proliferation assay was made using cell counting kit-8（CCK8）.The 8 μm pore-size transwell chamber and 4＇,6-diamidino-2-phenylindole（DAPI） staining were applied to examine the ability of invasion and migration of the cells.The protein expression of ERK1/2,zinc finger E-box-binding homeobox 1（ZEB1）,Scrib and lethal giant larvae homolog 2（Lgl2） was detected by Western blotting while the relative mRNA quantity of E-cadherin,N-cadherin,Occludin and junctional adhesion molecule-1（JAM1） was measured by realtime fluorescent quantitative polymerase chain reaction（RT-qPCR）.Results：XP induced a dose-dependent suppression on the proliferation of LoVo cells（P〈0.05 or P〈0.01）,with the inhibition rates varied from 27.30%to31.08%.Transwell assay showed that when preprocessed with PD98059 and XP-containing serum,the number of cells that passed the filter decreased significantly compared with that of NC group（P〈0.05 or P〈0.01）.Moreover,XP inhibited the protein expression of ERK1/2 and ZEB1（P〈0.05）;and up-regulated the protein expression of Scrib and Lgl2（P〈0.05）.The mRNA levels of E-cadherin,Occludin and JAM1 of the XP intervened groups and PC group markedly ascended（P〈0.05） while that of N-cadherin showed a descending tendency（P〉0.05）.Conclusion：XP intervention suppressed the ability of proliferation,invasion and migration of the LoVo cells.Regulating ZEB1-SCRIB Loop so as to recover epithelial phenotype and apical junctional complex might be one of the mechanisms by which XP produces the anti-metastasis effect.
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.
