RESUMEN
For harmonizing the contradiction of nanotheranostic agents between enhanced tumor accumulation and penetration, efficient cell internalization and fast elimination are key tactics for promoting their clinical applications. Herein, programmed stimuli-responsive poly(N-isopropylacrylamide)-carbon dot (PNIPAM-CD) hybrid nanogels are designed to address the abovementioned conflicts. The enlarged particle size of PNIPAM-CDs enables one to effectively improve their accumulation at tumor sites. Once the hybrid nanogels are docked in tumors and exposed to deep-red-light (660 nm) irradiation, heat and reactive oxygen species (ROS) are generated from the CDs, consequently activating photothermal therapy (PTT) and photodynamic therapy (PDT) effects and meanwhile inducing partial degradation of PNIPAM-CDs for deep tissue penetration. Further, enhanced cellular internalization of the functional components can be achieved owing to the pH-responsive charge reversal and temperature-dependent hydrophilic/hydrophobic conversion characteristics of PNIPAM-CDs. Finally, the overexpressed glutathione (GSH) in tumor cells would trigger further cleavage of the partially degraded hybrid nanogels, which is beneficial for their rapid clearance from the body. This work not only proposed a novel strategy to fabricate nanotheranostic agents using just a single functional component (i.e., the versatile CDs) to simplify the preparation process but also achieved effective delivery of agents into tumor cells by overcoming the multiple biological barriers to enhance therapeutic efficacy and decrease side effects.
Asunto(s)
Nanopartículas , Fotoquimioterapia , Carbono/química , Línea Celular Tumoral , Nanogeles , FototerapiaRESUMEN
Panax ginseng C.A. Meyer is one of the most highly valued medicinal plants in the world. To analyze the transcriptome of P. ginseng and discover the genes involved in ginsenoside biosynthesis, cDNAs derived from the total RNA of 11-year-old, wood-grown P. ginseng roots were analyzed by 454 sequencing. A total of 217,529 high quality reads (expressed sequence tags, ESTs), with an average length of 409 bases, were generated from a one-quarter run to yield 31,741 unique sequences. The majority (20,198; 63.6%) of the unique sequences were annotated using BLAST similarity searches. A total of 16,810 and 16,577 unique sequences were assigned to functional classifications and biochemical pathways based on Gene Ontology analysis and the Kyoto Encyclopedia of Genes and Genomes assignment, respectively. Nine genes involved in the biosynthesis of ginsenoside skeletons and many candidate genes putatively responsible for modification of the skeletons, including 133 cytochrome P450s and 235 glycosyltransferases, were identified. From these candidates, six transcripts encoding UDP-glycosyltransferases that were most likely to be involved in ginsenoside biosynthesis were selected. These results open a new avenue by which to explore and exploit biosynthetic and biochemical properties that may lead to drug improvement. These 454 ESTs will provide the foundation for further functional genomic research into the traditional herb P. ginseng or its closely related species.
Asunto(s)
Etiquetas de Secuencia Expresada , Ginsenósidos/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Panax/genética , Raíces de Plantas/genética , Sistema Enzimático del Citocromo P-450/genética , Biblioteca de Genes , Genes de Plantas , Ginsenósidos/biosíntesis , Glicosiltransferasas/genética , Estructura Molecular , Panax/química , Raíces de Plantas/química , ARN de Planta/genética , TranscriptomaRESUMEN
Two new compounds, named as sonchifolactone E (1) and sonchifolinin B (2), have been isolated from the whole plant of Ixeris sonchifolia, along with one known compound, sonchifolatone A (3). Their structures and stereochemistry were determined by spectroscopic methods.