PDF(Pubmed)
Abstract：
Macromolecular therapeutics such as nucleic acids, peptides, and proteins have the potential to overcome treatment barriers for cancer. For example, nucleic acid or peptide biologics may offer an alternative strategy for attacking otherwise undruggable therapeutic targets such as transcription factors and similar oncologic drivers. Delivery of biological therapeutics into tumor cells requires a robust system of cell penetration to access therapeutic targets within the cell interior. A highly effective means of accomplishing this may be borrowed from cell-penetrating pathogens such as viruses. In particular, the cell entry function of the adenovirus penton base capsid protein has been effective at penetrating tumor cells for the intracellular deposition of macromolecular therapies and membrane-impermeable drugs. Here, we provide an overview describing the evolution of tumor-targeted penton-base-derived nano-capsids as a framework for discussing the requirements for overcoming key barriers to macromolecular delivery. The development and pre-clinical testing of these proteins for therapeutic delivery has begun to also uncover the elusive mechanism underlying the membrane-penetrating function of the penton base. An understanding of this mechanism may unlock the potential for macromolecular therapeutics to be effectively delivered into cancer cells and to provide a treatment option for tumors resisting current clinical therapies.
摘要：
大分子治疗剂，如核酸，肽，和蛋白质有可能克服癌症的治疗障碍。例如,核酸或肽生物制剂可以提供一种替代策略，用于攻击否则不可用的治疗靶标，例如转录因子和类似的肿瘤驱动因子。将生物治疗剂递送到肿瘤细胞中需要强大的细胞穿透系统以进入细胞内部的治疗靶标。可以从细胞穿透病原体如病毒中借用实现这一点的高效手段。特别是,腺病毒五肽基衣壳蛋白的细胞进入功能在穿透肿瘤细胞中有效，用于大分子疗法和膜不透性药物的细胞内沉积。这里,我们提供了一个概述，描述了肿瘤靶向五酮基衍生的纳米衣壳的演变，作为讨论克服大分子递送关键障碍的要求的框架。用于治疗性递送的这些蛋白质的开发和临床前测试也开始揭示五肽碱的膜穿透功能的潜在机制。对该机制的理解可以解锁大分子治疗剂被有效地递送到癌细胞中并为抵抗当前临床疗法的肿瘤提供治疗选择的潜力。
