Enveloped RNA viruses are a group of viruses with an outer membrane derived from a host cell and a genome consisting of ribonucleic acid(RNA).These viruses rely on host cell machinery and organelles to replicate and a...Enveloped RNA viruses are a group of viruses with an outer membrane derived from a host cell and a genome consisting of ribonucleic acid(RNA).These viruses rely on host cell machinery and organelles to replicate and assemble new virus particles.However,the interaction between viruses and host organelles may be disrupted by nanomaterials,such as gold nanoparticles(AuNPs)with unique physical and chemical properties.In this study,we investigated the effects of AuNPs with different surface charge properties on the subcellular structure and function of mammalian cells,and their effects on two representative enveloped RNA viruses:lentivirus and human coronavirus OC43(HCoV-OC43)antiviral potential.By comparing the subcellular effects of AuNPs with different surface charge properties,we found that treatment with AuNPs with positive surface charges induced more significant disruption of subcellular structures than neutrally charged AuNPs and negatively charged AuNPs,mainly manifested in lysosomes and Cytoskeletal disorders.The antiviral effect of the surface positively charged AuNPs was further evaluated using lentivirus and HCoV-OC43.The results showed that AuNPs had a significant inhibitory effect on both lentivirus and HCoV-OC43 without obvious side effects.In conclusion,our study provides insights into the mechanism of action and biocompatibility of AuNP in biological systems,while supporting the potential of targeting organelle dynamics against enveloped RNA viruses.展开更多
Self-engineered small-molecule prodrug-nanoassemblies have emerged as promising nanomedicines for cancer treatment.Modular design of prodrug molecules is crucial to guarantee the favorable assembly stability,tumor-spe...Self-engineered small-molecule prodrug-nanoassemblies have emerged as promising nanomedicines for cancer treatment.Modular design of prodrug molecules is crucial to guarantee the favorable assembly stability,tumor-specific prodrug activation,and satisfactory antitumor effect.However,too much attention has been paid to the pharmacophores and chemical linkages in prodrug molecules while neglects the vital roles of nonpharmacological moieties.Herein,we found that iso-carbon fatty acids with different number,position,and cis-trans configuration of double bonds dramatically affect the nanoassembly feature and drug delivery fates of thioether-linked paclitaxel prodrug-nanoassemblies.Particularly,the number and cis-trans configuration of double bonds in fatty acid moieties not only dominate the self-assembly ability and colloidal stability of prodrugs,but also exert significant influences on the pharmacokinetics,prodrug activation,and antitumor activity of prodrug-nanoassemblies.Finally,oleic acid with one cis double bond stands out as the optimal nonpharmacological moiety for thioether-linked paclitaxel prodrugnanoassemblies.This study elucidates the crucial roles of nonpharmacological moieties in prodrugs,and provides new insights into the modular design of prodrug-based nanomedicines for cancer therapy.展开更多
基金This work was supported by the National Key Research&Development Program of China(grant Nos.2021YFA1201000 and 2018YFE0117800)the National Natural Science Foundation of China(grant No.82102204)+3 种基金National Natural Science Foundation of China(NSFC)key project(grant No.32030060)NSFC international collaboration key project(grant No.51861135103)The authors also appreciate the support of“the Beijing-Tianjin-Hebei Basic Research Cooperation Project”(19JCZDJC64100)the Science Fund for Creative Research Groups of Nature Science Foundation of Hebei Province(B2021201038).
文摘Enveloped RNA viruses are a group of viruses with an outer membrane derived from a host cell and a genome consisting of ribonucleic acid(RNA).These viruses rely on host cell machinery and organelles to replicate and assemble new virus particles.However,the interaction between viruses and host organelles may be disrupted by nanomaterials,such as gold nanoparticles(AuNPs)with unique physical and chemical properties.In this study,we investigated the effects of AuNPs with different surface charge properties on the subcellular structure and function of mammalian cells,and their effects on two representative enveloped RNA viruses:lentivirus and human coronavirus OC43(HCoV-OC43)antiviral potential.By comparing the subcellular effects of AuNPs with different surface charge properties,we found that treatment with AuNPs with positive surface charges induced more significant disruption of subcellular structures than neutrally charged AuNPs and negatively charged AuNPs,mainly manifested in lysosomes and Cytoskeletal disorders.The antiviral effect of the surface positively charged AuNPs was further evaluated using lentivirus and HCoV-OC43.The results showed that AuNPs had a significant inhibitory effect on both lentivirus and HCoV-OC43 without obvious side effects.In conclusion,our study provides insights into the mechanism of action and biocompatibility of AuNP in biological systems,while supporting the potential of targeting organelle dynamics against enveloped RNA viruses.
基金This work was financially supported by Shenyang Youth Science and Technology Innovation Talents Program(No.RC210452)the Liaoning Revitalization Talents Program(No.XLYC1907129)+1 种基金the Excellent Youth Science Foundation of Liaoning Province(No.2020-YQ-06)the China Postdoctoral Science Foundation(Nos.2020M670794 and 2021MD703858).
文摘Self-engineered small-molecule prodrug-nanoassemblies have emerged as promising nanomedicines for cancer treatment.Modular design of prodrug molecules is crucial to guarantee the favorable assembly stability,tumor-specific prodrug activation,and satisfactory antitumor effect.However,too much attention has been paid to the pharmacophores and chemical linkages in prodrug molecules while neglects the vital roles of nonpharmacological moieties.Herein,we found that iso-carbon fatty acids with different number,position,and cis-trans configuration of double bonds dramatically affect the nanoassembly feature and drug delivery fates of thioether-linked paclitaxel prodrug-nanoassemblies.Particularly,the number and cis-trans configuration of double bonds in fatty acid moieties not only dominate the self-assembly ability and colloidal stability of prodrugs,but also exert significant influences on the pharmacokinetics,prodrug activation,and antitumor activity of prodrug-nanoassemblies.Finally,oleic acid with one cis double bond stands out as the optimal nonpharmacological moiety for thioether-linked paclitaxel prodrugnanoassemblies.This study elucidates the crucial roles of nonpharmacological moieties in prodrugs,and provides new insights into the modular design of prodrug-based nanomedicines for cancer therapy.