Direct cytosolic delivery of large biomolecules that bypass the endocytic pathways is a promising strategy for therapeutic applications. Recent works have shown that small-molecule, nanoparticle, and polymer-based carriers can be designed for direct cytosolic delivery. It has been shown that the specific surface chemistry of the carrier, nanoscale assembly between the carrier and cargo molecule, good colloidal stability, and low surface charge of the nano-assembly are critical for non-endocytic uptake processes. Here we report a guanidinium-terminated polyaspartic acid micelle for direct cytosolic delivery of protein and DNA. The polymer delivers the protein/DNA directly to the cytosol by forming a nano-assembly, and it is observed that <200 nm size of colloidal assembly with near-zero surface charge is critical for efficient cytosolic delivery. This work shows the importance of size and colloidal property of the nano-assembly for carrier-based cytosolic delivery of large biomolecules.

中文翻译：

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通过胶体纳米组件与生物聚合物直接细胞传递外源遗传物质和蛋白质

绕过内吞途径的大生物分子的直接胞质递送是一种有前途的治疗应用策略。最近的工作表明，小分子、纳米颗粒和基于聚合物的载体可以设计用于直接胞质递送。已经表明，载体的特定表面化学、载体和货物分子之间的纳米级组装、良好的胶体稳定性和纳米组装的低表面电荷对于非内吞摄取过程至关重要。在这里，我们报告了一种胍终止的聚天冬氨酸胶束，用于直接在细胞溶质中传递蛋白质和 DNA。该聚合物通过形成纳米组装体将蛋白质/DNA 直接递送至胞质溶胶，据观察，具有接近零表面电荷的胶体组装体尺寸小于 200 nm，对于有效的胞质溶质递送至关重要。