Stimuli-resp on sive release of drugs from a nano carrier in spatial-,temporal-,and dosage-controlled fashi ons is of great interest in the pharmaceutical industry.Paclitaxel is one of the most effective and popular c...Stimuli-resp on sive release of drugs from a nano carrier in spatial-,temporal-,and dosage-controlled fashi ons is of great interest in the pharmaceutical industry.Paclitaxel is one of the most effective and popular chemotherapeutic drugs against a number of cancers such as metastatic or non metastatic breast can cer,non-small cell lung can cer,refractory ovaria n cancer,AIDS-related Kaposi's sarcoma,and head and neck can cers.Here,by taki ng the adva ntage of RNA nanotechno logy in biomedical and material scie nee,we developed a three-dime nsional pyramid-shaped RNA nanocage for a photocontrolled release of cargo,using paclitaxel as a model drug.The light-triggered release of paclitaxel or fluorophore Cy5 was achieved by incorporation of photocleavable spacers into the RNA nanoparticles.Upon irradiation with ultraviolet light,cargos were rapidly released(within 5 min).In vitro treatment of breast can cer cells with the RNA nano particles harbori ng photocleavable paclitaxel showed higher cytotoxicity as compared to RNA nanoparticles without the photocleavable spacer.The methodology provides proof of con cept for the applicati on of the light-triggered con trolled release of drugs from RNA nano cages.展开更多
Vascular remodeling is the essential pathogenic process of various cardiovascular disorders,including hypertension,atherosclerosis,stroke,and restenosis after vein graft.The main characterization of vascular remodelin...Vascular remodeling is the essential pathogenic process of various cardiovascular disorders,including hypertension,atherosclerosis,stroke,and restenosis after vein graft.The main characterization of vascular remodeling is abnormal variations of vascular cell phenotype,morphological structure and functions such as migration,hypertrophy,proliferation and apoptosis.Numerous researches revealed that mechanical stress,including shear stress and cyclic stretch,participates in physiological vascular homeostasis,or pathophysiological vascular remodeling.The understanding of mechanobiological mechanism in vascular remodeling will play a unique role in understanding human physiology and disease,and will generate important theoretical and clinical significance [2].Non-coding RNAs are newly recognized RNAs which cannot be translated into proteins but are involved in epigenetic modification of gene regulation.The studies revealed that non-coding RNAs,such as microRNAs(miRNAs)and long noncoding RNAs(long ncRNAs,IncRNA),as well as small interfering RNAs(siRNAs),piwi-interacting RNAs(piRNAs),small nucleolar RNAs(snoRNAs),play essential roles in the regulation of various processes,such as metabolism,development,cell proliferation,cell apoptosis,cell differentiation,oncogenesis and vascular homeostasis[5].However,the roles of non-coding RNAs in the cardiovascular system under mechanical stresses are still not clarified.Our recent researches detected the mechanical regulation of IncRNAs and miRNAs in vascular remodeling.LncRNAs are non-protein-coding transcripts that are longer than 200 nucleotides(nt),which is an arbitrary cut-off value that distinguishes these transcripts from other small RNAs.Unlike the well-established mechanism of microRNA action,the functional mode of IncRNAs is not fully understood.Increasing evidence shows that IncRNAs modulate gene expression via a multilevel-regulated pathway.Given their large number and complicated functional modes,lncRNAs are emerging as important regulators of a variety of cellular res展开更多
基金NIH grants R01EB019036,R01CA186100 and U01CA207946 to Peixuan Guo.The cryo-EM work was supported by NIH grants P41GM103832(W.C.)P50 GM103297(W C.).P.G.'s Sylvan G.Frank Endowed Chair position in Pharmaceutics and Drug Delivery is funded by the CM Chen Foundation.
文摘Stimuli-resp on sive release of drugs from a nano carrier in spatial-,temporal-,and dosage-controlled fashi ons is of great interest in the pharmaceutical industry.Paclitaxel is one of the most effective and popular chemotherapeutic drugs against a number of cancers such as metastatic or non metastatic breast can cer,non-small cell lung can cer,refractory ovaria n cancer,AIDS-related Kaposi's sarcoma,and head and neck can cers.Here,by taki ng the adva ntage of RNA nanotechno logy in biomedical and material scie nee,we developed a three-dime nsional pyramid-shaped RNA nanocage for a photocontrolled release of cargo,using paclitaxel as a model drug.The light-triggered release of paclitaxel or fluorophore Cy5 was achieved by incorporation of photocleavable spacers into the RNA nanoparticles.Upon irradiation with ultraviolet light,cargos were rapidly released(within 5 min).In vitro treatment of breast can cer cells with the RNA nano particles harbori ng photocleavable paclitaxel showed higher cytotoxicity as compared to RNA nanoparticles without the photocleavable spacer.The methodology provides proof of con cept for the applicati on of the light-triggered con trolled release of drugs from RNA nano cages.
基金supported by grants from the National Natural Science Foundation of China(11625209,11572199,31670958).
文摘Vascular remodeling is the essential pathogenic process of various cardiovascular disorders,including hypertension,atherosclerosis,stroke,and restenosis after vein graft.The main characterization of vascular remodeling is abnormal variations of vascular cell phenotype,morphological structure and functions such as migration,hypertrophy,proliferation and apoptosis.Numerous researches revealed that mechanical stress,including shear stress and cyclic stretch,participates in physiological vascular homeostasis,or pathophysiological vascular remodeling.The understanding of mechanobiological mechanism in vascular remodeling will play a unique role in understanding human physiology and disease,and will generate important theoretical and clinical significance [2].Non-coding RNAs are newly recognized RNAs which cannot be translated into proteins but are involved in epigenetic modification of gene regulation.The studies revealed that non-coding RNAs,such as microRNAs(miRNAs)and long noncoding RNAs(long ncRNAs,IncRNA),as well as small interfering RNAs(siRNAs),piwi-interacting RNAs(piRNAs),small nucleolar RNAs(snoRNAs),play essential roles in the regulation of various processes,such as metabolism,development,cell proliferation,cell apoptosis,cell differentiation,oncogenesis and vascular homeostasis[5].However,the roles of non-coding RNAs in the cardiovascular system under mechanical stresses are still not clarified.Our recent researches detected the mechanical regulation of IncRNAs and miRNAs in vascular remodeling.LncRNAs are non-protein-coding transcripts that are longer than 200 nucleotides(nt),which is an arbitrary cut-off value that distinguishes these transcripts from other small RNAs.Unlike the well-established mechanism of microRNA action,the functional mode of IncRNAs is not fully understood.Increasing evidence shows that IncRNAs modulate gene expression via a multilevel-regulated pathway.Given their large number and complicated functional modes,lncRNAs are emerging as important regulators of a variety of cellular res