Murthy Niren, Campbell Jean, Fausto Nelson, Hoffman Allan S, Stayton Patrick S
Department of Bioengineering, University of Washington, Seattle 98195, USA.
Bioconjug Chem. 2003 Mar-Apr;14(2):412-9. doi: 10.1021/bc020056d.
The biotechnology and pharmaceutical industries have developed a wide variety of potential therapeutics based on the molecules of biology: DNA, RNA, and proteins. While these therapeutics have tremendous potential, effectively formulating and delivering them have also been a widely recognized challenge. A variety of viruses and toxins have evolved multi-functional biomolecules to solve this problem by directing cellular uptake and enhancing biomolecular transport to the cytoplasm from the low pH endosomal compartment. In the study reported here, we have designed and synthesized bio-inspired, pH-responsive polymeric carriers, which we call "encrypted polymers", that mimic the multi-functional design of biology. These encrypted polymers target and direct cellular uptake, as well as enhance cytosolic delivery by disrupting endosomal membranes in a pH-dependent fashion. We show that the encrypted polymeric carriers significantly enhance the delivery of oligonucleotides and peptides to the cytoplasm of cultured macrophages, demonstrating the potential of this approach for delivery of biotherapeutics and vaccines.
生物技术和制药行业已经基于生物学分子（DNA、RNA和蛋白质）开发出了各种各样潜在的治疗方法。虽然这些治疗方法具有巨大潜力，但有效地配制和递送它们也一直是一个广为人知的挑战。多种病毒和毒素已经进化出多功能生物分子来解决这个问题，即通过引导细胞摄取并增强生物分子从低pH值的内体区室向细胞质的转运。在本文报道的研究中，我们设计并合成了受生物启发的、pH响应性聚合物载体，我们称之为“加密聚合物”，它模仿了生物学的多功能设计。这些加密聚合物靶向并引导细胞摄取，还通过以pH依赖的方式破坏内体膜来增强胞质递送。我们表明，加密聚合物载体显著增强了寡核苷酸和肽向培养的巨噬细胞细胞质的递送，证明了这种方法在递送生物治疗剂和疫苗方面的潜力。
