School of Materials Sciences, Indian Association for the Cultivation of Science, Kolkata 700032, India.
Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, College of Medicine, Chicago, Illinois 60612, United States.
ACS Appl Mater Interfaces. 2022 Jan 19;14(2):3199-3206. doi: 10.1021/acsami.1c22009. Epub 2022 Jan 5.
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.
直接将大生物分子递送到细胞质中，绕过内吞途径，是一种有前途的治疗应用策略。最近的研究表明，可以设计小分子、纳米颗粒和聚合物载体用于直接细胞质递送。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，我们报告了一种胍基封端的聚天冬氨酸胶束，用于蛋白质和 DNA 的直接细胞质递送。该聚合物通过形成纳米组装将蛋白质/DNA 直接递送到细胞质中，并且观察到具有近零表面电荷的<200nm 大小的胶体组装对于有效的细胞质递送至关重要。这项工作表明了纳米组装的大小和胶体性质对于基于载体的大生物分子细胞质递送的重要性。
