The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity a...The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity against various cancer cells.Although ADCs confer certain targeting properties to the toxins,low drug loading capacity,possible immunogenicity,and other drawbacks also limit the po-tential application of ADCs.Recently,non-ADC delivery strategies for toxins have been extensively investigated.To further understand the application of toxins in anti-tumor,this paper provided an over-view of prodrugs,nanodrug delivery systems,and biomimetic drug delivery systems.In addition,toxins and their combination strategies with other therapies were discussed.Finally,the prospect and challenge of toxins in cancertreatmentwerealso summarized.展开更多
Nanosuspensions,as a new drug delivery system for insoluble drugs,are only composed of a drug and a small amount of stabilizer,which is dispersed in an aqueous solution with high drug-loading,small particle size,high ...Nanosuspensions,as a new drug delivery system for insoluble drugs,are only composed of a drug and a small amount of stabilizer,which is dispersed in an aqueous solution with high drug-loading,small particle size,high dispersion,and large specific surface area.It can significantly improve the dissolution,bioavailability,and efficacy of insoluble drugs.In this study,paclitaxel nanosuspensions((PTX)NS)were prepared by an ultrasonic precipitation method,with the characteristics of simple preparation and easy repetition.With the help of a homologous targeting mechanism,a kind of glioma C6 cancer cell membrane(CCM)-coated(PTX)NS was developed and modified with DWSW peptide to obtain DWSW-CCM-(PTX)NS with the functions of BBB penetration and tumor targeting.The results showed that the cancer cell membrane could effectively camouflage the nanosuspensions so that it was not cleared by the immune system and could cross the blood-brain-barrier(BBB)and selectively target tumor tissues.Cell uptake experiments and in vivo imaging confirmed that the uptake of DWSW-CCM-(PTX)NS by tumor cells and the distribution in intracranial gliomas increased.Cytotoxicity test and in vivo anti-glioma studies showed that DWSW-CCM-(PTX)NS could significantly inhibit the growth of glioma cells and significantly prolong the survival time of glioma-bearing mice.Finally,the cancer cell membrane coating endowed the nanosuspensions with the biological properties of homologous adhesion and immune escape.This study provides an integrated solution for improving the targeting of nanosuspensions and demonstrates the encouraging potential of biomimetic nanosuspensions applicable to tumor therapy.展开更多
The glycosylphosphatidyl inositol(GPI)-anchored proteins are localized on the outer of the plasma membrane and clustered in membrane microdomain known as lipid rafts. Among them, mammalian alkaline phosphatase(AP) is ...The glycosylphosphatidyl inositol(GPI)-anchored proteins are localized on the outer of the plasma membrane and clustered in membrane microdomain known as lipid rafts. Among them, mammalian alkaline phosphatase(AP) is an enzyme widely distributed. So, it has important biological significance to study the combination of AP with lipid monolayer. In our work, the interaction between AP and sphingomyelin has been studied at the air-buffer interface as a biomimetic membrane system by the Langmuir film technique and atomic force microscopy. The surface pressure-area isotherm for the mixed alkaline phosphatase/sphingomyelin monolayer shown the presence of a transition from a liquid-expanded phase to the liquid-expanded/liquidcondensed coexist phase. And the surface compressional modulus suggested the mixed alkaline phosphatase/sphingomyelin monolayer has larger compressibility compared with the pure sphingomyelin monolayer. Besides, according to the micrographs, we inferred when combined with lipid monolayer at the air-buffer interface, the AP molecules formed polymer not multilayer or micelle. And, according to the limiting molecules area of AP, we inferred that 12 AP molecules formed a hexagon polymer unit.展开更多
Nature is providing inspiration for researchers to mimic its functions or existing structures,which could remarkably promote the development of new materials.Here,a large-size honeycomb-shaped liquid crystal elastomer...Nature is providing inspiration for researchers to mimic its functions or existing structures,which could remarkably promote the development of new materials.Here,a large-size honeycomb-shaped liquid crystal elastomer(LCE)actuator with LC orientation along the height of the honeycomb shape is built by combining magnetic field alignment and soft lithography technology.This homeotropic alignment allowed the height contraction of honeycomb and pore size expansion of hexagons in a reversible manner upon temperature variation.Therefore,this LCE actuator can be used as a structure for temperature-gated separation of particles.Another example is an iris-like LCE actuator,which has the capability of adjusting its aperture size with a temperature variation.Our approach provides a simple way to design customizable sophisticated LCE actuators for various potential applications.展开更多
基金support by the Shenzhen-Hong Kong-Macao Science and Technology Project(Category C)sponsored by the Science Technology and Innovation Committee of Shenzhen Municipality(SGDX20201103093003017)Shenzhen Key Basic Research Project(JCYJ20200109114827177)Hong Kong RGC General Research Fund(CityU 11216421).
基金This work was supported by the National Postdoctoral Foundation of China(No.2023M730375)Liaoning Province Department of Education Project(No.LJKMZ20221365,China)+3 种基金the State Key Laboratory of Natural and Biomimetic Drugs(No.K202215,China)the National Natural Science Foundation of China(No.82173766)Liaoning Province Applied Basic Research Program(No.2022JH2/101300097,China)the Natural Science Foundation of Shandong Province(No.ZR2021QH084,China)。
文摘The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity against various cancer cells.Although ADCs confer certain targeting properties to the toxins,low drug loading capacity,possible immunogenicity,and other drawbacks also limit the po-tential application of ADCs.Recently,non-ADC delivery strategies for toxins have been extensively investigated.To further understand the application of toxins in anti-tumor,this paper provided an over-view of prodrugs,nanodrug delivery systems,and biomimetic drug delivery systems.In addition,toxins and their combination strategies with other therapies were discussed.Finally,the prospect and challenge of toxins in cancertreatmentwerealso summarized.
基金We are grateful for the financial support from National Natural Science Foundation of China(Grant No.82073783).
文摘Nanosuspensions,as a new drug delivery system for insoluble drugs,are only composed of a drug and a small amount of stabilizer,which is dispersed in an aqueous solution with high drug-loading,small particle size,high dispersion,and large specific surface area.It can significantly improve the dissolution,bioavailability,and efficacy of insoluble drugs.In this study,paclitaxel nanosuspensions((PTX)NS)were prepared by an ultrasonic precipitation method,with the characteristics of simple preparation and easy repetition.With the help of a homologous targeting mechanism,a kind of glioma C6 cancer cell membrane(CCM)-coated(PTX)NS was developed and modified with DWSW peptide to obtain DWSW-CCM-(PTX)NS with the functions of BBB penetration and tumor targeting.The results showed that the cancer cell membrane could effectively camouflage the nanosuspensions so that it was not cleared by the immune system and could cross the blood-brain-barrier(BBB)and selectively target tumor tissues.Cell uptake experiments and in vivo imaging confirmed that the uptake of DWSW-CCM-(PTX)NS by tumor cells and the distribution in intracranial gliomas increased.Cytotoxicity test and in vivo anti-glioma studies showed that DWSW-CCM-(PTX)NS could significantly inhibit the growth of glioma cells and significantly prolong the survival time of glioma-bearing mice.Finally,the cancer cell membrane coating endowed the nanosuspensions with the biological properties of homologous adhesion and immune escape.This study provides an integrated solution for improving the targeting of nanosuspensions and demonstrates the encouraging potential of biomimetic nanosuspensions applicable to tumor therapy.
基金Foundamental Research Funds for the Central Universities(GK201402010)the Natural Science Basic Research Plan in Shaanxi Province of China(2012JQ1002)Innovation Funds of Graduate Programs,SNU(2012CXS033)for supporting this work
文摘The glycosylphosphatidyl inositol(GPI)-anchored proteins are localized on the outer of the plasma membrane and clustered in membrane microdomain known as lipid rafts. Among them, mammalian alkaline phosphatase(AP) is an enzyme widely distributed. So, it has important biological significance to study the combination of AP with lipid monolayer. In our work, the interaction between AP and sphingomyelin has been studied at the air-buffer interface as a biomimetic membrane system by the Langmuir film technique and atomic force microscopy. The surface pressure-area isotherm for the mixed alkaline phosphatase/sphingomyelin monolayer shown the presence of a transition from a liquid-expanded phase to the liquid-expanded/liquidcondensed coexist phase. And the surface compressional modulus suggested the mixed alkaline phosphatase/sphingomyelin monolayer has larger compressibility compared with the pure sphingomyelin monolayer. Besides, according to the micrographs, we inferred when combined with lipid monolayer at the air-buffer interface, the AP molecules formed polymer not multilayer or micelle. And, according to the limiting molecules area of AP, we inferred that 12 AP molecules formed a hexagon polymer unit.
基金This study received support from the French National Research Agency(ANR-16-CE29-0028)from the“Institut Pierre-Gilles de Gennes”(IPGG,laboratoire d’excellence,“Investissements d’avenir”programs ANR-10-IDEX-0001-02 PSL,ANR10-LABX-31 and ANR10-EQPX-34).
文摘Nature is providing inspiration for researchers to mimic its functions or existing structures,which could remarkably promote the development of new materials.Here,a large-size honeycomb-shaped liquid crystal elastomer(LCE)actuator with LC orientation along the height of the honeycomb shape is built by combining magnetic field alignment and soft lithography technology.This homeotropic alignment allowed the height contraction of honeycomb and pore size expansion of hexagons in a reversible manner upon temperature variation.Therefore,this LCE actuator can be used as a structure for temperature-gated separation of particles.Another example is an iris-like LCE actuator,which has the capability of adjusting its aperture size with a temperature variation.Our approach provides a simple way to design customizable sophisticated LCE actuators for various potential applications.