AIM： To investigate the anti-angiogenic and antitumor activities of recombinant vascular basement membrane-derived multifunctional peptide （rVBMDMP） in hepatocellular carcinoma （HCC）. METHODS： HepG2, Bel-7402, H...AIM： To investigate the anti-angiogenic and antitumor activities of recombinant vascular basement membrane-derived multifunctional peptide （rVBMDMP） in hepatocellular carcinoma （HCC）. METHODS： HepG2, Bel-7402, Hep-3B, HUVE-12 and L-02 cell lines were cultured in vitro and the inhibitory effect of rVBMDMP on proliferation of cells was detected by MTT assay. The in vivo antitumor efficacy of rVBMDMP on HCC was assessed by HepG2 xenografts in nude mice. Distribution of rVBMDMP, mechanism by which the growth of HepG2 xenografts is inhibited, and microvessel area were observed by proliferating cell nuclear antigen （PCNA） and CD31 immunohistochemistry. RESULTS： MTT assay showed that rVBMDMP markedly inhibited the proliferation of human HCC （HepG2, Bel-7402, Hep-3B） cells and human umbilical vein endothelial （HUVE-12） cells in a dose-dependent manner, with little effect on the growth of L-02 cells. When the ICs0 was 4.68, 7.65, 8.96, 11.65 and 64.82 μmol/L, respectively, the potency of rVBMDMP to HepG2 cells was similar to 5-fluorouracil （5-FU） with an IC50 of 4.59 μmol/L. The selective index of cytotoxicity to HepG2 cells of rVBMDMP was 13.8 （64.82/4.68）, which was higher than that of 5-FU [SI was 1.9 （8.94/4.59）]. The VEGF-targeted recombinant humanized monoclonal antibody bevacizumab （100 mg/L） did not affect the proliferation of HepG2, Bel-7402, Hep-3B and L-02 cells, but the growth inhibitory rate of bevacizumab （100 mg/L） to HUVE-12 cells was 87.6% ± 8.2%. AIternis diebus intraperitoneal injection of rVBMDMP suppressed the growth of HepG2 xenografts in a dose-dependent manner, rVBMDMP （1, 3, 10 mg/kg） decreased the tumor weight by 12.6%, 55.9% and 79.7%, respectively, compared with the vehicle control. Immunohistochemical staining of rVBMDMP showed that the positive area rates （2.2% ± 0.73%, 4.5%± 1.3% and 11.5% ±3.8%） in rVBMDMP treated group （1, 3, 10 mg/kg） were significantly higher than that （0.13% ± 0.04%） in the control group （P 〈 0.01）. The positive area rates （19.0% ± 5.7%, 12.2% ± 3.5% and 5.2% ±1.6% ） of PCNA in rVBMDMP treated group （1, 3, 10 mg/kg） were significantly lower than that （29.5% ± 9.4%） in the control group （P 〈 0.05）. rVBMDMP at doses of 1, 3 and 10 mg/kg significantly reduced the tumor microvessel area levels （0.26%± 0.07%, 0.12% ± 0.03% and 0.05% ± 0.01% vs 0.45% ± 0.15%） in HepG2 xenografts （P 〈 0.01）, as assessed by CD31 staining. CONCLUSION： rVBMDMP has effective and unique anti-tumor properties, and is a promising candidate for the development of anti-tumor drugs.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
Cell membrane-derived nanovesicles(CMNVs)are nanoscale lipid bilayer structures obtained from cellular membranes that serve as biomimetic drug delivery platforms,offering immune evasion,targeting,and surface functiona...Cell membrane-derived nanovesicles(CMNVs)are nanoscale lipid bilayer structures obtained from cellular membranes that serve as biomimetic drug delivery platforms,offering immune evasion,targeting,and surface functionalization capabilities.While most CMNVs originate from mammalian cells,Toxoplasma gondii(T.gondii),a genetically tractable protozoan with a structurally distinct membrane,offers a high-yield and underexplored source for producing T.gondii-derived CMNVs(TgCMNVs).These vesicles are obtained from the parasite’s plasma membrane and inner membrane complex and retain unique features including abundant GPI-anchored SRS proteins,phosphatidylthreonine-rich lipids,and an editable genome,enabling versatile engineering via genetic and chemical strategies.We review methods for TgCMNV fabrication,purification,and functionalization,and evaluate their potential in immunomodulation,attenuation of tissue injury,cancer immunotherapy,and self-adjuvanting vaccine design.By combining intrinsic immune engagement with programmable surface architec-ture,TgCMNVs could serve as a complementary and adaptable platform alongside established CMNV systems.Finally,we discuss key translational considerations,including scalable production,immunogenicity control,regulatory compliance,and stability testing,which will be essential for assessing the feasibility of TgCMNVs in clinical applications.展开更多
基金Supported by The Nation Natural Science Foundation of China, No. 30472040the Key Program of the Health Department of Hunan Province, No. 2004-005the National Undergraduate Innovative Test Program, No. YA07059 and No. 081054239
文摘AIM： To investigate the anti-angiogenic and antitumor activities of recombinant vascular basement membrane-derived multifunctional peptide （rVBMDMP） in hepatocellular carcinoma （HCC）. METHODS： HepG2, Bel-7402, Hep-3B, HUVE-12 and L-02 cell lines were cultured in vitro and the inhibitory effect of rVBMDMP on proliferation of cells was detected by MTT assay. The in vivo antitumor efficacy of rVBMDMP on HCC was assessed by HepG2 xenografts in nude mice. Distribution of rVBMDMP, mechanism by which the growth of HepG2 xenografts is inhibited, and microvessel area were observed by proliferating cell nuclear antigen （PCNA） and CD31 immunohistochemistry. RESULTS： MTT assay showed that rVBMDMP markedly inhibited the proliferation of human HCC （HepG2, Bel-7402, Hep-3B） cells and human umbilical vein endothelial （HUVE-12） cells in a dose-dependent manner, with little effect on the growth of L-02 cells. When the ICs0 was 4.68, 7.65, 8.96, 11.65 and 64.82 μmol/L, respectively, the potency of rVBMDMP to HepG2 cells was similar to 5-fluorouracil （5-FU） with an IC50 of 4.59 μmol/L. The selective index of cytotoxicity to HepG2 cells of rVBMDMP was 13.8 （64.82/4.68）, which was higher than that of 5-FU [SI was 1.9 （8.94/4.59）]. The VEGF-targeted recombinant humanized monoclonal antibody bevacizumab （100 mg/L） did not affect the proliferation of HepG2, Bel-7402, Hep-3B and L-02 cells, but the growth inhibitory rate of bevacizumab （100 mg/L） to HUVE-12 cells was 87.6% ± 8.2%. AIternis diebus intraperitoneal injection of rVBMDMP suppressed the growth of HepG2 xenografts in a dose-dependent manner, rVBMDMP （1, 3, 10 mg/kg） decreased the tumor weight by 12.6%, 55.9% and 79.7%, respectively, compared with the vehicle control. Immunohistochemical staining of rVBMDMP showed that the positive area rates （2.2% ± 0.73%, 4.5%± 1.3% and 11.5% ±3.8%） in rVBMDMP treated group （1, 3, 10 mg/kg） were significantly higher than that （0.13% ± 0.04%） in the control group （P 〈 0.01）. The positive area rates （19.0% ± 5.7%, 12.2% ± 3.5% and 5.2% ±1.6% ） of PCNA in rVBMDMP treated group （1, 3, 10 mg/kg） were significantly lower than that （29.5% ± 9.4%） in the control group （P 〈 0.05）. rVBMDMP at doses of 1, 3 and 10 mg/kg significantly reduced the tumor microvessel area levels （0.26%± 0.07%, 0.12% ± 0.03% and 0.05% ± 0.01% vs 0.45% ± 0.15%） in HepG2 xenografts （P 〈 0.01）, as assessed by CD31 staining. CONCLUSION： rVBMDMP has effective and unique anti-tumor properties, and is a promising candidate for the development of anti-tumor drugs.
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supported in part by grants from the National Natural Science Foundation of China(82470719)High-level Medical Team Project in Baoan,Shenzhen(202401).
文摘Cell membrane-derived nanovesicles(CMNVs)are nanoscale lipid bilayer structures obtained from cellular membranes that serve as biomimetic drug delivery platforms,offering immune evasion,targeting,and surface functionalization capabilities.While most CMNVs originate from mammalian cells,Toxoplasma gondii(T.gondii),a genetically tractable protozoan with a structurally distinct membrane,offers a high-yield and underexplored source for producing T.gondii-derived CMNVs(TgCMNVs).These vesicles are obtained from the parasite’s plasma membrane and inner membrane complex and retain unique features including abundant GPI-anchored SRS proteins,phosphatidylthreonine-rich lipids,and an editable genome,enabling versatile engineering via genetic and chemical strategies.We review methods for TgCMNV fabrication,purification,and functionalization,and evaluate their potential in immunomodulation,attenuation of tissue injury,cancer immunotherapy,and self-adjuvanting vaccine design.By combining intrinsic immune engagement with programmable surface architec-ture,TgCMNVs could serve as a complementary and adaptable platform alongside established CMNV systems.Finally,we discuss key translational considerations,including scalable production,immunogenicity control,regulatory compliance,and stability testing,which will be essential for assessing the feasibility of TgCMNVs in clinical applications.
