No abstract

RNA interference mediated by small interfering RNA (siRNA) provides a powerful tool for gene regulation, and has a broad potential as a promising therapeutic strategy. However, therapeutics based on siRNA have had limited clinical success due to their undesirable pharmacokinetic properties. This study presents pH‐sensitive nanoparticles‐based siRNA delivery systems (PNSDS), which are positive‐charge‐free nanocarriers, composed of siRNA chemically crosslinked with multi‐armed poly(ethylene glycol) carriers via acid‐labile acetal linkers. The unique siRNA crosslinked structure of PNSDS allows it to have minimal cytotoxicity, high siRNA loading efficiency, and a stimulus‐responsive property that enables the selective intracellular release of siRNA in response to pH conditions. This study demonstrates that PNSDS can deliver tumor necrosis factor alpha (TNF‐α) siRNA into macrophages and induce the efficient down regulation of the targeted gene in complete cell culture media. Moreover, PNSDS with mannose targeting moieties can selectively accumulate in mice liver, induce specific inhibition of macrophage TNF‐α expression in vivo, and consequently protect mice from inflammation‐induced liver damages. Therefore, this novel siRNA delivering platform would greatly improve the therapeutic potential of RNAi based therapies.

Panax notoginseng (Burkill) F.H.Chen (Araliaceae), of which the dry root and rhizome are precious traditional Chinese medicine, suffers severely from diseases during planting. Essential oils (EOs) with antimicrobial activity are a possibility for the development of green pesticides. We extracted EOs from Pogostemon cablin (Blanco) Benth. and Eupatorium fortunei Turcz., respectively and tested their inhibitory rates on fungi isolated from diseased P. notoginseng by the Oxford cup method. The compounds of the EO were identified by GC/MS and the minimum inhibitory concentrations (MICs) of the EOs and their main components were evaluated by the 96-well plate method. We also mixed P. cablin EO, E. fortunei EO and hymexazol in pairs to explore whether their combinations produce stronger antifungal effects than individual components. Finally, we evaluated the effects of the EOs against Fusarium oxysporum in vivo. P. cablin EO and E. fortunei EO exhibited different antifungal activities against fungi, with the inhibitory rates of 21.02 %-100 % and 54.84 %-100 % and MICs of 0.07-0.88 mg/mL and 0.20-1.17 mg/mL, respectively. Pogostone (24.96 %) and thymol (15.64 %) were the major compounds of P. cablin EO and E. fortunei EO, respectively, and they exhibited stronger antifungal activities than EOs, with MICs of 0.008-0.078 mg/mL and 0.12-0.31 mg/mL, respectively. Moreover, hymexazol was mixed with E. fortunei EO, and the inhibitory effect against Cylindrocarpon destructans was enhanced with a synergistic effect. The disease incidence and disease index of EO treatments decreased significantly in vivo. Based on our study, P. cablin EO and E. fortunei EO have great potential to be developed into green fungicides for use in agriculture to control diseases of P. notoginseng.