PDF(Pubmed)
Abstract：
The delivery of therapeutic agents faces significant hurdles posed by the endo-lysosomal pathway, a bottleneck that hampers clinical effectiveness. This comprehensive review addresses the urgent need to enhance cellular delivery mechanisms to overcome these obstacles. It focuses on the potential of smart nanomaterials, delving into their unique characteristics and mechanisms in detail. Special attention is given to their ability to strategically evade endosomal entrapment, thereby enhancing therapeutic efficacy. The manuscript thoroughly examines assays crucial for understanding endosomal escape and cellular uptake dynamics. By analyzing various assessment methods, we offer nuanced insights into these investigative approaches\' multifaceted aspects. We meticulously analyze the use of smart nanocarriers, exploring diverse mechanisms such as pore formation, proton sponge effects, membrane destabilization, photochemical disruption, and the strategic use of endosomal escape agents. Each mechanism\'s effectiveness and potential application in mitigating endosomal entrapment are scrutinized. This paper provides a critical overview of the current landscape, emphasizing the need for advanced delivery systems to navigate the complexities of cellular uptake. Importantly, it underscores the transformative role of smart nanomaterials in revolutionizing cellular delivery strategies, leading to a paradigm shift towards improved therapeutic outcomes.
摘要：
治疗剂的递送面临由内溶酶体途径造成的重大障碍，阻碍临床有效性的瓶颈。这项全面的审查解决了增强细胞递送机制以克服这些障碍的迫切需要。它专注于智能纳米材料的潜力，详细研究其独特的特征和机制。特别注意它们战略性地逃避内体截留的能力，从而提高治疗效果。手稿彻底检查了对理解内体逃逸和细胞摄取动力学至关重要的测定。通过分析各种评估方法，我们为这些调查方法提供了多方面的细致入微的见解。我们仔细分析智能纳米载体的使用，探索不同的机制，如孔隙形成，质子海绵效应，膜失稳，光化学破坏，以及内体逃逸剂的战略用途。仔细研究了每种机制在减轻内体截留中的有效性和潜在应用。本文提供了当前景观的关键概述，强调需要先进的递送系统来驾驭细胞摄取的复杂性。重要的是,它强调了智能纳米材料在彻底改变细胞递送策略中的变革作用，导致范式转向改善治疗结果。
