Abstract：
Although biomacromolecules are promising cytosolic drugs which have attracted tremendous attention, the major obstacles were the cellular membrane hindering the entrance and the endosome entrapment inducing biomacromolecule degradation. How to avoid those limitations to realize directly cytosolic delivery was still a challenge. Here, we prepared oligoarginine modified lipid to assemble a nanovesicle for biomacromolecules delivery, including mRNA (mRNA) and proteins which could be directly delivered into the cytoplasm of dendritic cells through subendocytosis-mediated membrane fusion. We named this membrane fusion lipid nanovesicle as MF-LNV. The mRNA loaded MF-LNV as nanovaccines showed efficient antigen expression to elicit robust immuno responses for cancer therapy. What\'s more, the antigen protein loaded MF-LNV as nanovaccines elicits much stronger CD8+ T cell specific responses than lipid nanoparticles through normal uptake pathways. This MF-LNV represented a refreshing strategy for intracellular delivery of the biomacromolecule.
摘要：
尽管生物大分子是有前途的胞浆药物，引起了极大的关注，主要障碍是细胞膜阻碍入口和内体截留诱导生物大分子降解。如何避免这些限制以实现直接胞质递送仍然是一个挑战。这里,我们制备了寡精氨酸修饰的脂质以组装用于生物大分子递送的纳米囊泡，包括mRNA（mRNA）和可以通过亚胞吞介导的膜融合直接递送到树突状细胞的细胞质中的蛋白质。我们将这种膜融合脂质纳米囊命名为MF-LNV。作为纳米疫苗的负载mRNA的MF-LNV显示出有效的抗原表达以引发用于癌症治疗的稳健免疫应答。更重要的是，负载抗原蛋白的MF-LNV作为纳米疫苗通过正常摄取途径比脂质纳米颗粒引起更强的CD8+T细胞特异性应答。该MF-LNV代表了用于生物大分子的细胞内递送的更新策略。
