Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs(siRNAs), an important class of nucleic acid drugs, can si...Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs(siRNAs), an important class of nucleic acid drugs, can silence the m RNAs of tumor-associated genes with high specificity through RNA interference(RNAi), inhibiting tumor-related signaling pathways or protein expression and thereby exerting anti-tumor effects. However, antitumor siRNA drugs are currently in the clinical research stage, and none of these drugs have been approved for marketing, mainly because of the challenges in terms of safety,efficacy and targeted delivery. Nano-delivery systems can enhance siRNA stability and improve siRNA pharmacokinetics and biodistribution, while increasing their uptake by target cells to achieve precise delivery and controlled release, thereby serving as a promising solution to overcome the challenges of siRNA drug application. This review summarizes the existing research on the nano-delivery systems currently available to help siRNAs achieve organ-targeted delivery and enhance the anti-tumor efficacy of siRNAs, discussing the characteristics of siRNA action and the unique advantages of different types of nanodelivery systems. The aim was to provide novel ideas for the design and optimization of siRNA-based drug delivery and the development of novel anti-tumor formulations to promote the clinical translation and application of siRNA drugs.展开更多
Asthma, one of the most prevalent chronic inflammatory diseases, remains challenging to manage effectively. Current therapies commonly alleviate symptoms through broad immunosuppression and bronchodilation but fail to...Asthma, one of the most prevalent chronic inflammatory diseases, remains challenging to manage effectively. Current therapies commonly alleviate symptoms through broad immunosuppression and bronchodilation but fail to target disease-specific molecular pathways. Genetic intervention using small interfering RNA(siRNA) has emerged as a promising strategy for asthma therapy. However, its success is largely hindered by the lack of an efficient delivery approach targeting airway epithelial cells(AECs). Here, we developed a novel inhalable siRNA delivery system based on artificially prepared nanovesicles through designed extrusion processes of mesenchymal stem cells. To enable an effective inhalation delivery of siRNA via nanovesicles, various parameters, including extrusion cycles,membrane pore sizes, and centrifugal forces were examined through orthogonal testing.Results revealed that the artificially prepared nanovesicles demonstrated remarkable capability to deliver thymic stromal lymphopoietin-targeted siRNA into AECs and substantially suppressed the inflammatory pathways and goblet cell hyperplasia, and eventually achieved a significant inhibition of asthma symptoms in ovalbumin-induced asthma models. Thus, the present study provides a novel nebulized nanovesicle-based carrier for effective delivery of siRNA through local inhalation, offering a promising therapeutic delivery platform for asthma and potentially other respiratory diseases.展开更多
近日,北京大学药学院天然药物及仿生药物全国重点实验室王坚成教授团队在药剂学领域顶刊Journal of Controlled Release在线发表了题为“Nintedanib-amplified Effects of HSP47 siRNA on Liver Fibrosis Therapy by Inhibiting Collage...近日,北京大学药学院天然药物及仿生药物全国重点实验室王坚成教授团队在药剂学领域顶刊Journal of Controlled Release在线发表了题为“Nintedanib-amplified Effects of HSP47 siRNA on Liver Fibrosis Therapy by Inhibiting Collagen Secretion”的研究论文。该研究开发了一种尼达尼布(Nintedanib, NDNB)与HSP47 siRNA共递送的脂质纳米颗粒系统(LNP-siHSP47/NDNB),实现了通过“双通路抑制胶原分泌”协同增强肝纤维化治疗的策略。展开更多
RNA干扰在癌症和其他多种疾病的治疗中具有广阔的应用前景,亟需发展高效、安全的递送手段来实现RNA干扰技术的临床应用。本研究使用瞬时纳米沉淀技术,制备系列稳定的、基于壳聚糖(CS)和三聚磷酸钠(TPP)的纳米粒子,系统研究了CS浓度、分...RNA干扰在癌症和其他多种疾病的治疗中具有广阔的应用前景,亟需发展高效、安全的递送手段来实现RNA干扰技术的临床应用。本研究使用瞬时纳米沉淀技术,制备系列稳定的、基于壳聚糖(CS)和三聚磷酸钠(TPP)的纳米粒子,系统研究了CS浓度、分子量及其与TPP的质量比对CS/TPP纳米粒子的物理化学性质的影响,并初步评价了纳米粒子的基因沉默效率。结果显示,CS浓度为0.3~0.6 g/L和CS/TPP质比为1/1~4/1时,可以形成较为稳定的复合物。其中,CS浓度为0.5g/L,质量比为2/1时可得到直径为70~100 nm的稳定纳米粒子。稳定的CS/TPP纳米粒子对siRNA的负载效率为75%~90%,细胞毒性低。在2.5 ng siRNA/μL浓度下,负载siRNA的CS/TPP纳米粒子可以引起约30%的目的基因的沉默。相关结果对制备稳定的、小尺寸CS纳米粒子及其siRNA递送研究具有一定的借鉴意义。展开更多
基金supported by the National Natural Science Foundation of China (No. 82373809 to Y.L., No. 825B2116 to J.L., No. 82373805 to N.Z., No. 82204295 to W.M)the Shandong Excellent Youth Fund and Provincial Natural Science Foundation (ZR2022YQ76 to Y.L., ZR2022QH224 to W.M.)。
文摘Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs(siRNAs), an important class of nucleic acid drugs, can silence the m RNAs of tumor-associated genes with high specificity through RNA interference(RNAi), inhibiting tumor-related signaling pathways or protein expression and thereby exerting anti-tumor effects. However, antitumor siRNA drugs are currently in the clinical research stage, and none of these drugs have been approved for marketing, mainly because of the challenges in terms of safety,efficacy and targeted delivery. Nano-delivery systems can enhance siRNA stability and improve siRNA pharmacokinetics and biodistribution, while increasing their uptake by target cells to achieve precise delivery and controlled release, thereby serving as a promising solution to overcome the challenges of siRNA drug application. This review summarizes the existing research on the nano-delivery systems currently available to help siRNAs achieve organ-targeted delivery and enhance the anti-tumor efficacy of siRNAs, discussing the characteristics of siRNA action and the unique advantages of different types of nanodelivery systems. The aim was to provide novel ideas for the design and optimization of siRNA-based drug delivery and the development of novel anti-tumor formulations to promote the clinical translation and application of siRNA drugs.
基金supported by National Natural Science Foundation of China (U22A20383)Natural Science Foundation of Zhejiang Province (LY24H300001)+2 种基金Fundamental Research Funds for the Central Universities (226-2022-00125)Zhejiang Province Postdoctoral Research Excellence Funding Project (ZJ2023151)Pharmacy 80 Basic Research Funding in College of Pharmaceutical Sciences, Zhejiang University Education Foundation。
文摘Asthma, one of the most prevalent chronic inflammatory diseases, remains challenging to manage effectively. Current therapies commonly alleviate symptoms through broad immunosuppression and bronchodilation but fail to target disease-specific molecular pathways. Genetic intervention using small interfering RNA(siRNA) has emerged as a promising strategy for asthma therapy. However, its success is largely hindered by the lack of an efficient delivery approach targeting airway epithelial cells(AECs). Here, we developed a novel inhalable siRNA delivery system based on artificially prepared nanovesicles through designed extrusion processes of mesenchymal stem cells. To enable an effective inhalation delivery of siRNA via nanovesicles, various parameters, including extrusion cycles,membrane pore sizes, and centrifugal forces were examined through orthogonal testing.Results revealed that the artificially prepared nanovesicles demonstrated remarkable capability to deliver thymic stromal lymphopoietin-targeted siRNA into AECs and substantially suppressed the inflammatory pathways and goblet cell hyperplasia, and eventually achieved a significant inhibition of asthma symptoms in ovalbumin-induced asthma models. Thus, the present study provides a novel nebulized nanovesicle-based carrier for effective delivery of siRNA through local inhalation, offering a promising therapeutic delivery platform for asthma and potentially other respiratory diseases.
文摘近日,北京大学药学院天然药物及仿生药物全国重点实验室王坚成教授团队在药剂学领域顶刊Journal of Controlled Release在线发表了题为“Nintedanib-amplified Effects of HSP47 siRNA on Liver Fibrosis Therapy by Inhibiting Collagen Secretion”的研究论文。该研究开发了一种尼达尼布(Nintedanib, NDNB)与HSP47 siRNA共递送的脂质纳米颗粒系统(LNP-siHSP47/NDNB),实现了通过“双通路抑制胶原分泌”协同增强肝纤维化治疗的策略。
文摘RNA干扰在癌症和其他多种疾病的治疗中具有广阔的应用前景,亟需发展高效、安全的递送手段来实现RNA干扰技术的临床应用。本研究使用瞬时纳米沉淀技术,制备系列稳定的、基于壳聚糖(CS)和三聚磷酸钠(TPP)的纳米粒子,系统研究了CS浓度、分子量及其与TPP的质量比对CS/TPP纳米粒子的物理化学性质的影响,并初步评价了纳米粒子的基因沉默效率。结果显示,CS浓度为0.3~0.6 g/L和CS/TPP质比为1/1~4/1时,可以形成较为稳定的复合物。其中,CS浓度为0.5g/L,质量比为2/1时可得到直径为70~100 nm的稳定纳米粒子。稳定的CS/TPP纳米粒子对siRNA的负载效率为75%~90%,细胞毒性低。在2.5 ng siRNA/μL浓度下,负载siRNA的CS/TPP纳米粒子可以引起约30%的目的基因的沉默。相关结果对制备稳定的、小尺寸CS纳米粒子及其siRNA递送研究具有一定的借鉴意义。
