In vitro and in vivo mRNA delivery using lipid-enveloped pH-responsive polymer nanoparticles.
In vitro and in vivo mRNA delivery using lipid-enveloped pH-responsive polymer nanoparticles.
复制标题
体外和体内mRNA使用脂质开发的pH响应性聚合物纳米颗粒。
DOI：
10.1021/mp100390w
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发表时间：
2011-06-06
影响因子：
4.9
通讯作者：
Irvine DJ
中科院分区：
文献类型：
--
作者：
Su X;Fricke J;Kavanagh DG;Irvine DJ
开发了具有由磷脂双层壳包封的聚（β-氨基酯）（PBAE）核的生物可降解核-壳结构的纳米颗粒用于体内mRNA递送，以期递送基于mRNA的疫苗。选择pH响应性PBAE组分以促进内体破坏，而选择脂质表面层以使聚阳离子核心的毒性最小化。信使RNA通过静电相互作用被有效地吸附到这些净正电荷纳米颗粒的表面上。在体外，树突状细胞（DC）的mRNA负载颗粒的摄取导致mRNA以低细胞毒性递送到胞质溶胶中，随后在这些难以转染的细胞中以约30%的频率翻译编码的蛋白。在小鼠中鼻内施用的负载有mRNA的颗粒导致在施用后6小时即在体内表达报告蛋白荧光素酶，该时间点是当裸mRNA经鼻内施用时，面无表情。在随后的时间点，在裸mRNA处理的小鼠中检测到荧光素酶表达，但与颗粒处理的小鼠相比，该组显示出转染水平的广泛变化。因此，该系统可能是有前途的基于mRNA的疫苗的非侵入性递送。
Biodegradable core-shell structured nanoparticles with a poly(β-amino-ester) (PBAE) core enveloped by a phospholipid bilayer shell were developed for in vivo mRNA delivery, with a view toward delivery of mRNA-based vaccines. The pH-responsive PBAE component was chosen to promote endosome disruption, while the lipid surface layer was selected to minimize toxicity of the polycation core. Messenger RNA was efficiently adsorbed via electrostatic interactions onto the surface of these net positively-charged nanoparticles. In vitro, mRNA-loaded particle uptake by dendritic cells (DCs) led to mRNA delivery into the cytosol with low cytotoxicity, followed by translation of the encoded protein in these difficult-to-transfect cells at a frequency of ~30%. Particles loaded with mRNA administered intranasally in mice led to the expression of the reporter protein luciferase in vivo as soon as 6 h after administration, a timepoint when naked mRNA given i.n. showed no expression. At later timepoints, luciferase expression was detected in naked mRNA-treated mice, but this group showed a wide variation in levels of transfection, compared to particle-treated mice. This system may thus be promising for non-invasive delivery of mRNA-based vaccines.
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影响因子：
3.7
作者：
Fernández-Urrusuno, R;Calvo, P;Alonso, MJ
通讯作者：
Alonso, MJ
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
3.9
作者：
Currie, EPK;Sieval, AB;Stuart, MAC
通讯作者：
Stuart, MAC
DOI：
10.1073/pnas.84.8.2449
发表时间：
1987-04-01
影响因子：
11.1
作者：
CZERKINSKY, C;PRINCE, SJ;MESTECKY, J
通讯作者：
MESTECKY, J
影响因子：
5.1
作者：
Brunner, S;Sauer, T;Wagner, E
通讯作者：
Wagner, E