Messenger RNA(mRNA)is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases,including viral infection and cancer.Especially,mRNA-based vaccines,as a new type ...Messenger RNA(mRNA)is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases,including viral infection and cancer.Especially,mRNA-based vaccines,as a new type of vaccine,have played a leading role in fighting against the current global pandemic of COVID-19.However,the inherent drawbacks,including large size,negative charge,and instability,hinder its use as a therapeutic agent.Lipid carriers are distinguishable and promising vehicles for mRNA delivery,owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time.Here,we first summarized the structure and properties of different lipid carriers,such as liposomes,liposome-like nanoparticles,solid lipid nanoparticles,lipid-polymer hybrid nanoparticles,nanoemulsions,exosomes and lipoprotein particles,and their applications in delivering mRNA.Then,the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted.Recent advancements in the mRNA vaccine of COVID-19 were emphasized.Finally,we described our future vision and perspectives in this field.展开更多
A polymeric polyethylenimine(PEI)-based prodrug of anticancer doxorubicin(DOX)(PEI-hyd-DOX) was designed by attaching DOX to PEI via an acid-labile hydrazone bond, for the achievement of biocontrollable gene and drug ...A polymeric polyethylenimine(PEI)-based prodrug of anticancer doxorubicin(DOX)(PEI-hyd-DOX) was designed by attaching DOX to PEI via an acid-labile hydrazone bond, for the achievement of biocontrollable gene and drug co-delivery in response to the intracellular acid microenvironments in the late endosome/lysosome compartments. The cytotoxicity of PEI-hyd-DOX was evaluated by the MTT assay and the cellular uptake was monitored using confocal laser scanning microscopy. The polymeric prodrug can respond with a high sensitivity to the specific acid condition inside cells, thus permitting the precise biocontrol over intracellular drug liberation with high drug efficacy. The chemical attachment of drug molecules also led to the relatively reduced toxicity and the enhanced transfection efficiency compared with parent PEI. The resulting data adumbrated the potential of PEI-hyd-DOX to co-deliver DOX and therapeutic gene for the combination of chemotherapy and gene therapy.展开更多
背景:纳米材料是抗肿瘤药物的理想载体,具有重要的科学价值和应用价值,为临床抗肿瘤提供了新的有效手段。目的:系统评价纳米给药系统在肿瘤靶向治疗的基础研究及临床应用。方法:以"nanoparticle,cancer,drug delivery system,nanot...背景:纳米材料是抗肿瘤药物的理想载体,具有重要的科学价值和应用价值,为临床抗肿瘤提供了新的有效手段。目的:系统评价纳米给药系统在肿瘤靶向治疗的基础研究及临床应用。方法:以"nanoparticle,cancer,drug delivery system,nanotube,nanosphere"为关键词,计算机检索北美临床试验注册中心及Web of Science数据库2000-01-01/2012-12-31发表的纳米给药系统在肿瘤靶向治疗相关临床试验注册项目及文献。根据纳入与排除标准筛选文献,将检索结果以注册号、注册题目、项目状态、干预措施、试验的申办者、试验的疾病种类导出进行评价质量及文献分析。结果与结论:①北美临床试验注册中心关于纳米给药系统在肿瘤靶向治疗的相关临床试验研究开始于1999年,共检索到注册项目489项,经查阅后,共有429项纳入了分析。美国注册的纳米载体肿瘤靶向给药临床试验项目最多,共112项,其次为加拿大24项。中国注册的临床试验有22项,其中大陆注册8项,香港地区注册4项,台湾地区注册10项。研究的注册数量2003年跌至谷底,只有5项注册项目,之后数量大幅度升高,在2008年注册项目数量达到顶峰,为56项。2008年后,注册的项目数量处于波动状态。②北美临床试验注册中心纳米给药系统在肿瘤靶向治疗的相关临床试验项目样本量在1-2000之间,以50人以下的小样本研究为主。研究的肿瘤类型以乳腺癌为主,其次为内分泌腺瘤及淋巴瘤。③2000-01-01/2012-12-31在Web of Science数据库发表的纳米载体肿瘤靶向给药相关文章4497篇,其中,美国发文量占总数比重最大(66.42%),发表文章2987篇。高被引文章主要发表在Proceedings of the National Academy of Sciences of the United States of America(《美国科学院院刊》)。展开更多
基金supported by the National Natural Science Foundation of China(Nos.81872823,82073782)the Double First-Class(CPU2018PZQ13,China)of the CPU+2 种基金the Shanghai Science and Technology Committee(19430741500,China)Natural Science Foundation of the Jiangsu Higher Education Institutions of China(21KJA320003)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(zdsys-202103)。
文摘Messenger RNA(mRNA)is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases,including viral infection and cancer.Especially,mRNA-based vaccines,as a new type of vaccine,have played a leading role in fighting against the current global pandemic of COVID-19.However,the inherent drawbacks,including large size,negative charge,and instability,hinder its use as a therapeutic agent.Lipid carriers are distinguishable and promising vehicles for mRNA delivery,owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time.Here,we first summarized the structure and properties of different lipid carriers,such as liposomes,liposome-like nanoparticles,solid lipid nanoparticles,lipid-polymer hybrid nanoparticles,nanoemulsions,exosomes and lipoprotein particles,and their applications in delivering mRNA.Then,the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted.Recent advancements in the mRNA vaccine of COVID-19 were emphasized.Finally,we described our future vision and perspectives in this field.
基金supported by the National Natural Science Foundation of China (21374085, 21174110, 51233003)the Natural Science Foundation of Hubei Province of China (2014CFB697)the Fundamental Research Funds for the Central Universities (2042014kf0193)
文摘A polymeric polyethylenimine(PEI)-based prodrug of anticancer doxorubicin(DOX)(PEI-hyd-DOX) was designed by attaching DOX to PEI via an acid-labile hydrazone bond, for the achievement of biocontrollable gene and drug co-delivery in response to the intracellular acid microenvironments in the late endosome/lysosome compartments. The cytotoxicity of PEI-hyd-DOX was evaluated by the MTT assay and the cellular uptake was monitored using confocal laser scanning microscopy. The polymeric prodrug can respond with a high sensitivity to the specific acid condition inside cells, thus permitting the precise biocontrol over intracellular drug liberation with high drug efficacy. The chemical attachment of drug molecules also led to the relatively reduced toxicity and the enhanced transfection efficiency compared with parent PEI. The resulting data adumbrated the potential of PEI-hyd-DOX to co-deliver DOX and therapeutic gene for the combination of chemotherapy and gene therapy.
文摘背景:纳米材料是抗肿瘤药物的理想载体,具有重要的科学价值和应用价值,为临床抗肿瘤提供了新的有效手段。目的:系统评价纳米给药系统在肿瘤靶向治疗的基础研究及临床应用。方法:以"nanoparticle,cancer,drug delivery system,nanotube,nanosphere"为关键词,计算机检索北美临床试验注册中心及Web of Science数据库2000-01-01/2012-12-31发表的纳米给药系统在肿瘤靶向治疗相关临床试验注册项目及文献。根据纳入与排除标准筛选文献,将检索结果以注册号、注册题目、项目状态、干预措施、试验的申办者、试验的疾病种类导出进行评价质量及文献分析。结果与结论:①北美临床试验注册中心关于纳米给药系统在肿瘤靶向治疗的相关临床试验研究开始于1999年,共检索到注册项目489项,经查阅后,共有429项纳入了分析。美国注册的纳米载体肿瘤靶向给药临床试验项目最多,共112项,其次为加拿大24项。中国注册的临床试验有22项,其中大陆注册8项,香港地区注册4项,台湾地区注册10项。研究的注册数量2003年跌至谷底,只有5项注册项目,之后数量大幅度升高,在2008年注册项目数量达到顶峰,为56项。2008年后,注册的项目数量处于波动状态。②北美临床试验注册中心纳米给药系统在肿瘤靶向治疗的相关临床试验项目样本量在1-2000之间,以50人以下的小样本研究为主。研究的肿瘤类型以乳腺癌为主,其次为内分泌腺瘤及淋巴瘤。③2000-01-01/2012-12-31在Web of Science数据库发表的纳米载体肿瘤靶向给药相关文章4497篇,其中,美国发文量占总数比重最大(66.42%),发表文章2987篇。高被引文章主要发表在Proceedings of the National Academy of Sciences of the United States of America(《美国科学院院刊》)。
