Lymphoma is a hematological malignancy with an increasing mortality rate.Nevertheless,the treatment strategy against lymphoma remains limited.Doxorubicin(DOX)is a broad-spectrum anti-tumor chemotherapeutic drug,the cl...Lymphoma is a hematological malignancy with an increasing mortality rate.Nevertheless,the treatment strategy against lymphoma remains limited.Doxorubicin(DOX)is a broad-spectrum anti-tumor chemotherapeutic drug,the clinical application of which is limited by serious adverse effects and drug resistance.In this work,biodegradable methoxy poly(ethylene glycol)-block-poly(lactic acid)(mPEG-PLA)nanomicelles co-delivering of DOX and apatinib(AP)(DOX-AP/m)was developed for lymphoma therapy.The average particle size of the self-assembled drug-loaded nano-micelle was 31.94 nm.It is revealed that AP can enhance the uptake of DOX by tumor cells.The in vivo and in vitro experimental results revealed that DOX-AP/m combination therapy could inhibit proliferation and promote apoptosis of lymphoma cells,and greatly suppress tumor growth.Our study indicated that DOX-AP/m might provide new insight and hold great potential in the treatment of lymphoma.展开更多
Finding more effective and safe non-viral vectors to transfer genes into cancer cells has become the key of immune gene therapy for cancer.Herein a triblock compound MPEG_(2000)-PDLLA_(4000)-MPEG_(2000) modified by ca...Finding more effective and safe non-viral vectors to transfer genes into cancer cells has become the key of immune gene therapy for cancer.Herein a triblock compound MPEG_(2000)-PDLLA_(4000)-MPEG_(2000) modified by cationic liposome DOTAP was used as a non-viral vector DOTAP/MPEG_(2000)-PDLLA_(4000)-MPEG_(2000)(DMPM)to effectively transfer interleukin(IL)-12 plasmid(pIL-12)into tumor tissue.IL-12 produced by transfected tumor cells successfully inducing lymphocyte proliferation and promoting interferon-γ(IFN-γ)secretion,which resulted in tumor cells death.The ability of DMPM to transfer pIL-12 and the immune effect induced by IL-12 in cells had been explored.The anti-tumor effect,mechanism and safety of pIL-12/DMPM in mice cancer model were investigated in this study.Our results showed that the pIL-12 transferred by DMPM was highly expressed both in CT26 cells and B16-F10 cells.IL-12 expressed in the culture supernatant of transfected tumor cells stimulated lymphocyte proliferation and promoted IFN-γsecretion.The experimental result confirmed that pIL-12/DMPM therapy significantly reduced tumor growth in mice model.We designed the nanocomposite DMPM to deliver pIL-12 for cancer treatment and explored its therapeutic efficacy and the underlying anti-tumor mechanism.Our study suggested pIL-12 loaded by DMPM complex would be an effective strategy for cancer treatment.展开更多
Cancer remains a significant risk to human health.Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation.Nanomedicine shows great potential for cancer diagnosis and treatme...Cancer remains a significant risk to human health.Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation.Nanomedicine shows great potential for cancer diagnosis and treatment.Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations.Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors.The achievement of targeted medication delivery in cancer therapy can be accomplished through the rational design and manufacture of nanodrug carriers.Nanoparticles have the capability to effectively transport medications or gene fragments to tumor tissues via passive or active targeting processes,thus enhancing treatment outcomes while minimizing harm to healthy tissues.Simultaneously,nanoparticles can be employed in the context of radiation sensitization and photothermal therapy to enhance the therapeutic efficacy of malignant tumors.This review presents a literature overview and summary of how nanotechnology is used in the diagnosis and treatment of malignant tumors.According to oncological diseases originating from different systems of the body and combining the pathophysiological features of cancers at different sites,we review the most recent developments in nanotechnology applications.Finally,we briefly discuss the prospects and challenges of nanotechnology in cancer.展开更多
Triple-negative breast cancer(TNBC)is the most challenging subtype of breast cancer.Various endeavor has been made to explore the molecular biology basis of TNBC.Herein,we reported a novel function of factor Kinectin ...Triple-negative breast cancer(TNBC)is the most challenging subtype of breast cancer.Various endeavor has been made to explore the molecular biology basis of TNBC.Herein,we reported a novel function of factor Kinectin 1(KTN1)as a carcinogenic promoter in TNBC.KTN1 expression in TNBC was increased compared with adjacent tissues or luminal or Her2 subtypes of breast cancer,and TNBC patients with high KTN1 expression have poor prognosis.In functional studies,knockdown of KTN1 inhibited the proliferation and invasiveness of TNBC both in vitro and in vivo,while overexpression of KTN1 promoted cancer cell proliferation and invasiveness.RNA-seq analysis revealed that the interaction of cytokine-cytokine receptor,particularly CXCL8 gene,was upregulated by KTN1,which was supported by the further experiments.CXCL8 depletion inhibited the tumorigenesis and progression of TNBC.Additionally,rescue experiments validated that KTN1-mediated cell growth acceleration in TNBC was dependent on CXCL8 both in vitro and in vivo.Furthermore,it was found that KTN1 enhanced the phosphorylation of NF-κB/p65 protein at Ser536 site,and specifically bound to NF-κB/p65 protein in the nucleus and cytoplasm of cells.Moreover,the transcription of CXCL8 gene was directly upregulated by the complex of KTN1 and NF-κB/p65 protein.Taken together,our results elucidated a novel mechanism of KTN1 gene in TNBC tumorigenesis and progression.KTN1 may be a potential molecular target for the development of TNBC treatment.展开更多
The immunosuppressive tumor microenvironment(TME)of cancer strongly hinders the anti-tumor immune responses,thereby resulting in disappointing responses to immunotherapy.Chemoattractive and promotive traits of chemoki...The immunosuppressive tumor microenvironment(TME)of cancer strongly hinders the anti-tumor immune responses,thereby resulting in disappointing responses to immunotherapy.Chemoattractive and promotive traits of chemokines exerted on leukocytes have garnered interest in improving the efficiency of immunotherapy by increasing the infiltration of immune cells in the TME.In this study,a folic acid(FA)-modified gene delivery system based on the self-assembly of DOTAP,MPEG-PCL-MPEG,and FA-PEG-PCL-PEG-FA,namely F-PPPD,was developed to deliver plasmids encoding the immunostimulating chemokine CKb11.The delivery of plasmid CKb11(pCKb11)by F-PPPD nanoparticles resulted in the high secretion of CKb11 from tumor cells,which successfully activated T cells,suppressed the M2 polarization of macrophages,promoted the maturation of dendritic cells(DCs),facilitated the infiltration of natural killer(NK)cells and inhibited the infiltration of immunosuppressive cells in tumor tissues.Administration of F-PPPD/pCKb11 also significantly suppressed the cancer progression.Our study demonstrated a nanotechnology-enabled delivery of pCKb11,that remodeled the immunosuppressive TME,for cancer treatment.展开更多
Immunosuppression tumor microenvironment(TME)seriously impedes anti-tumor immune response,resulting in poor immunotherapy effect of cancer.This study develops a folate-modified delivery system to transport the plasmid...Immunosuppression tumor microenvironment(TME)seriously impedes anti-tumor immune response,resulting in poor immunotherapy effect of cancer.This study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells,resulting in high CKb11 secretion from tumor cells,successfully activating immune cells and increasing cytokine secretion to reshape the TME,and ultimately delaying tumor progression.The chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in TME.It can cause high expression of IFN-γ,which is a double-edged sword that inhibits tumor growth while causing an increase in the expression of PD-L1 on tumor cells.Therefore,combining CKb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense,leading to a collaborative anti-tumor outcome.Thus,utilizing nanotechnology to achieve targeted delivery of immune stimulatory chemokines and immune checkpoint inhibitors to tumor sites,thereby reshaping immunosuppressive TME for cancer treatment,has great potential as an immunogene therapy in clinical applications.展开更多
基金supported by the National Natural Science Foundation of China(Nos.32222046,82172630)。
文摘Lymphoma is a hematological malignancy with an increasing mortality rate.Nevertheless,the treatment strategy against lymphoma remains limited.Doxorubicin(DOX)is a broad-spectrum anti-tumor chemotherapeutic drug,the clinical application of which is limited by serious adverse effects and drug resistance.In this work,biodegradable methoxy poly(ethylene glycol)-block-poly(lactic acid)(mPEG-PLA)nanomicelles co-delivering of DOX and apatinib(AP)(DOX-AP/m)was developed for lymphoma therapy.The average particle size of the self-assembled drug-loaded nano-micelle was 31.94 nm.It is revealed that AP can enhance the uptake of DOX by tumor cells.The in vivo and in vitro experimental results revealed that DOX-AP/m combination therapy could inhibit proliferation and promote apoptosis of lymphoma cells,and greatly suppress tumor growth.Our study indicated that DOX-AP/m might provide new insight and hold great potential in the treatment of lymphoma.
基金supported by the National Natural Science Foundation of China(No.81972347)the Key R&D Projects of the Science and Technology Department of Sichuan Province(No.2022YFS0324).
文摘Finding more effective and safe non-viral vectors to transfer genes into cancer cells has become the key of immune gene therapy for cancer.Herein a triblock compound MPEG_(2000)-PDLLA_(4000)-MPEG_(2000) modified by cationic liposome DOTAP was used as a non-viral vector DOTAP/MPEG_(2000)-PDLLA_(4000)-MPEG_(2000)(DMPM)to effectively transfer interleukin(IL)-12 plasmid(pIL-12)into tumor tissue.IL-12 produced by transfected tumor cells successfully inducing lymphocyte proliferation and promoting interferon-γ(IFN-γ)secretion,which resulted in tumor cells death.The ability of DMPM to transfer pIL-12 and the immune effect induced by IL-12 in cells had been explored.The anti-tumor effect,mechanism and safety of pIL-12/DMPM in mice cancer model were investigated in this study.Our results showed that the pIL-12 transferred by DMPM was highly expressed both in CT26 cells and B16-F10 cells.IL-12 expressed in the culture supernatant of transfected tumor cells stimulated lymphocyte proliferation and promoted IFN-γsecretion.The experimental result confirmed that pIL-12/DMPM therapy significantly reduced tumor growth in mice model.We designed the nanocomposite DMPM to deliver pIL-12 for cancer treatment and explored its therapeutic efficacy and the underlying anti-tumor mechanism.Our study suggested pIL-12 loaded by DMPM complex would be an effective strategy for cancer treatment.
基金supported by the National Natural Science Foundation of China(Nos.82172643,32222046 and 32371545,China)the Sichuan Science and Technology Program(No.2023NSFSC1931,China)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21022,China).
文摘Cancer remains a significant risk to human health.Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation.Nanomedicine shows great potential for cancer diagnosis and treatment.Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations.Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors.The achievement of targeted medication delivery in cancer therapy can be accomplished through the rational design and manufacture of nanodrug carriers.Nanoparticles have the capability to effectively transport medications or gene fragments to tumor tissues via passive or active targeting processes,thus enhancing treatment outcomes while minimizing harm to healthy tissues.Simultaneously,nanoparticles can be employed in the context of radiation sensitization and photothermal therapy to enhance the therapeutic efficacy of malignant tumors.This review presents a literature overview and summary of how nanotechnology is used in the diagnosis and treatment of malignant tumors.According to oncological diseases originating from different systems of the body and combining the pathophysiological features of cancers at different sites,we review the most recent developments in nanotechnology applications.Finally,we briefly discuss the prospects and challenges of nanotechnology in cancer.
基金This work was supported by grants from the China Postdoctoral Science Foundation Grant 2019M660232(Lin Gao)the National Natural Science Foundation of China 82002929(Lin Gao)+7 种基金Basic and Applied Basic Research Foundation of Guangdong Province[2020A1515111072(Un Gao),2019B151512003(Chang Zou),2020B1515120032(Chang Zou)]the Science and Technology Foundation of Shenzhen JCYJ20190806154610953(Lin Gao),JCYJ20180305164128430(Chang Zou)the International Cooperation Foundation of Shenzhen GJHZ20180928171602104(Chang Zou)the Shenzhen Economic and Information Committee"Innovation Chain and Industry Chain"integration special support plan project 20180225112449943(Chang Zou)the Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis(Chang Zou)the Ministry of Science and Technology of the People’s Republic of China(No.2018ZX09201018)the National Natural Science Foundation of China(No.81803183)the Shenzhen Key Medical Discipline Construction Fund(SZXK053).
文摘Triple-negative breast cancer(TNBC)is the most challenging subtype of breast cancer.Various endeavor has been made to explore the molecular biology basis of TNBC.Herein,we reported a novel function of factor Kinectin 1(KTN1)as a carcinogenic promoter in TNBC.KTN1 expression in TNBC was increased compared with adjacent tissues or luminal or Her2 subtypes of breast cancer,and TNBC patients with high KTN1 expression have poor prognosis.In functional studies,knockdown of KTN1 inhibited the proliferation and invasiveness of TNBC both in vitro and in vivo,while overexpression of KTN1 promoted cancer cell proliferation and invasiveness.RNA-seq analysis revealed that the interaction of cytokine-cytokine receptor,particularly CXCL8 gene,was upregulated by KTN1,which was supported by the further experiments.CXCL8 depletion inhibited the tumorigenesis and progression of TNBC.Additionally,rescue experiments validated that KTN1-mediated cell growth acceleration in TNBC was dependent on CXCL8 both in vitro and in vivo.Furthermore,it was found that KTN1 enhanced the phosphorylation of NF-κB/p65 protein at Ser536 site,and specifically bound to NF-κB/p65 protein in the nucleus and cytoplasm of cells.Moreover,the transcription of CXCL8 gene was directly upregulated by the complex of KTN1 and NF-κB/p65 protein.Taken together,our results elucidated a novel mechanism of KTN1 gene in TNBC tumorigenesis and progression.KTN1 may be a potential molecular target for the development of TNBC treatment.
基金the Ministry of Science and Technology of the People’s Republic of China(No.2018ZX09201018)Sichuan Science and Technology Program(No.2019YFS0089,2019YFS0340 and 2020YFS0217)+4 种基金the China Postdoctoral Science Foundation(No.2020M680150)full-time postdoctoral research and development fund of Sichuan University(No.20826041D4048)the full-time postdoctoral research and development fund of West China Hospital of Sichuan University(No.2020HXBH059 and No.2020HXBH002)1·3·5 project of excellent development of discipline of West China Hospital of Sichuan University(No.ZYYC21005)the Natural Science Foundation Youth Project of Jiangsu Province(BK20190989).
文摘The immunosuppressive tumor microenvironment(TME)of cancer strongly hinders the anti-tumor immune responses,thereby resulting in disappointing responses to immunotherapy.Chemoattractive and promotive traits of chemokines exerted on leukocytes have garnered interest in improving the efficiency of immunotherapy by increasing the infiltration of immune cells in the TME.In this study,a folic acid(FA)-modified gene delivery system based on the self-assembly of DOTAP,MPEG-PCL-MPEG,and FA-PEG-PCL-PEG-FA,namely F-PPPD,was developed to deliver plasmids encoding the immunostimulating chemokine CKb11.The delivery of plasmid CKb11(pCKb11)by F-PPPD nanoparticles resulted in the high secretion of CKb11 from tumor cells,which successfully activated T cells,suppressed the M2 polarization of macrophages,promoted the maturation of dendritic cells(DCs),facilitated the infiltration of natural killer(NK)cells and inhibited the infiltration of immunosuppressive cells in tumor tissues.Administration of F-PPPD/pCKb11 also significantly suppressed the cancer progression.Our study demonstrated a nanotechnology-enabled delivery of pCKb11,that remodeled the immunosuppressive TME,for cancer treatment.
基金supported by Sichuan Science and Technology Program(No.2023YFS0170,2023NSFSC1931)supported by Medical Science and Technology Project of Sichuan Provincial Health Commission(No.21PJ009)+2 种基金supported by the National Natural Science Foundation of China(No.32222046,32371545,82103635)supported by the Technological innovation research and development project of Chengdu Science and Technology Bureau(2022-YF05-01589-SN)The 1⋅3⋅5 project of excellent development of discipline of West China Hospital of Sichuan University(No.ZYGC21022).
文摘Immunosuppression tumor microenvironment(TME)seriously impedes anti-tumor immune response,resulting in poor immunotherapy effect of cancer.This study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells,resulting in high CKb11 secretion from tumor cells,successfully activating immune cells and increasing cytokine secretion to reshape the TME,and ultimately delaying tumor progression.The chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in TME.It can cause high expression of IFN-γ,which is a double-edged sword that inhibits tumor growth while causing an increase in the expression of PD-L1 on tumor cells.Therefore,combining CKb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense,leading to a collaborative anti-tumor outcome.Thus,utilizing nanotechnology to achieve targeted delivery of immune stimulatory chemokines and immune checkpoint inhibitors to tumor sites,thereby reshaping immunosuppressive TME for cancer treatment,has great potential as an immunogene therapy in clinical applications.
