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Nanoassemblies designed for efficient nuclear targeting
Advanced Drug Delivery Reviews ( IF 15.2 ) Pub Date : 2024-06-09 , DOI: 10.1016/j.addr.2024.115354 Michal Skowicki 1 , Shabnam Tarvirdipour 2 , Manuel Kraus 2 , Cora-Ann Schoenenberger 1 , Cornelia G Palivan 1
Advanced Drug Delivery Reviews ( IF 15.2 ) Pub Date : 2024-06-09 , DOI: 10.1016/j.addr.2024.115354 Michal Skowicki 1 , Shabnam Tarvirdipour 2 , Manuel Kraus 2 , Cora-Ann Schoenenberger 1 , Cornelia G Palivan 1
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One of the key aspects of coping efficiently with complex pathological conditions is delivering the desired therapeutic compounds with precision in both space and time. Therefore, the focus on nuclear-targeted delivery systems has emerged as a promising strategy with high potential, particularly in gene therapy and cancer treatment. Here, we explore the design of supramolecular nanoassemblies as vehicles to deliver specific compounds to the nucleus, with the special focus on polymer and peptide-based carriers that expose nuclear localization signals. Such nanoassemblies aim at maximizing the concentration of genetic and therapeutic agents within the nucleus, thereby optimizing treatment outcomes while minimizing off-target effects. A complex scenario of conditions, including cellular uptake, endosomal escape, and nuclear translocation, requires fine tuning of the nanocarriers’ properties. First, we introduce the principles of nuclear import and the role of nuclear pore complexes that reveal strategies for targeting nanosystems to the nucleus. Then, we provide an overview of cargoes that rely on nuclear localization for optimal activity as their integrity and accumulation are crucial parameters to consider when designing a suitable delivery system. Considering that they are in their early stages of research, we present various cargo-loaded peptide- and polymer nanoassemblies that promote nuclear targeting, emphasizing their potential to enhance therapeutic response. Finally, we briefly discuss further advancements for more precise and effective nuclear delivery.
中文翻译：
专为高效核靶向而设计的纳米组件
有效应对复杂病理状况的关键方面之一是在空间和时间上精确地提供所需的治疗化合物。因此，对核靶向递送系统的关注已成为一种具有巨大潜力的有前途的策略，特别是在基因治疗和癌症治疗方面。在这里，我们探索超分子纳米组件的设计作为将特定化合物传递到细胞核的载体，特别关注暴露核定位信号的聚合物和基于肽的载体。这种纳米组件旨在最大限度地提高细胞核内遗传和治疗药物的浓度，从而优化治疗结果，同时最大限度地减少脱靶效应。复杂的条件场景，包括细胞摄取、内体逃逸和核易位，需要对纳米载体的特性进行微调。首先，我们介绍了核输入的原理和核孔复合物的作用，揭示了将纳米系统靶向细胞核的策略。然后，我们概述了依赖核定位来实现最佳活性的货物，因为它们的完整性和积累是设计合适的输送系统时需要考虑的关键参数。考虑到它们还处于研究的早期阶段，我们提出了各种促进核靶向的负载肽和聚合物纳米组件，强调了它们增强治疗反应的潜力。最后，我们简要讨论了更精确、更有效的核运载的进一步进展。
更新日期：2024-06-09
中文翻译：
专为高效核靶向而设计的纳米组件
有效应对复杂病理状况的关键方面之一是在空间和时间上精确地提供所需的治疗化合物。因此，对核靶向递送系统的关注已成为一种具有巨大潜力的有前途的策略，特别是在基因治疗和癌症治疗方面。在这里，我们探索超分子纳米组件的设计作为将特定化合物传递到细胞核的载体，特别关注暴露核定位信号的聚合物和基于肽的载体。这种纳米组件旨在最大限度地提高细胞核内遗传和治疗药物的浓度，从而优化治疗结果，同时最大限度地减少脱靶效应。复杂的条件场景，包括细胞摄取、内体逃逸和核易位，需要对纳米载体的特性进行微调。首先，我们介绍了核输入的原理和核孔复合物的作用，揭示了将纳米系统靶向细胞核的策略。然后，我们概述了依赖核定位来实现最佳活性的货物，因为它们的完整性和积累是设计合适的输送系统时需要考虑的关键参数。考虑到它们还处于研究的早期阶段，我们提出了各种促进核靶向的负载肽和聚合物纳米组件，强调了它们增强治疗反应的潜力。最后，我们简要讨论了更精确、更有效的核运载的进一步进展。
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