Nanoparticles (NPs) are one of the leading and promising technologies for gene and drug delivery. However, despite continuous advancements in the delivery of NPs, endosomal escape remains a major issue and a matter of grave concern for developing an efficient and targeted delivery system for therapeutic applications. Most of NPs generally follow endocytic pathway for internalization into the cells. Following the internalization process, NPs must escape into the cell cytoplasm for evading degradation by hydrolytic enzymes present in the lysosomes. Various types of lipids have been used in the past viz. fusogenic lipid dioleoylphosphatidylethanolamine (DOPE), pH-sensitive lipids, cationic lipid and multiple charges containing lipid to escape from endosomes. Recently, several novel polymers, pH-sensitive peptides, proteins and many others endosomolytic agents have been identified and developed for incorporating into gene and drug delivery system to facilitate endosomal escape. In this review, endosomal escape mechanisms of different types of NPs have been discussed in detail and compared with endosomal escape mechanisms of viruses and other synthetic gene delivery systems to escape from endosomes. Also, the designing of endosomolytic agents to facilitate endosomal escape based on different approaches and strategies is explored. Moreover, this review article highlights the recent advancements in the development of NPs equipped with endosomolytic agents including its future directions and applications in the field of nanomedicine.

纳米颗粒（NPs）是基因和药物递送的领先和有前途的技术之一。然而，尽管NPs的递送不断进步，但是内体逃逸仍然是主要问题，并且对于开发用于治疗应用的有效且靶向的递送系统而言，是一个令人严重关注的问题。大多数NP通常遵循内吞途径内化进入细胞。在内部化过程之后，NP必须逃逸到细胞质中才能逃避溶酶体中存在的水解酶的降解。过去已经使用了各种类型的脂质。融合脂质二油酰基磷脂酰乙醇胺（DOPE），pH敏感脂质，阳离子脂质和含有脂质的多种电荷从内体中逸出。最近，已经鉴定并开发了几种新颖的聚合物，pH敏感肽，蛋白质和许多其他内溶体试剂，以整合到基因和药物输送系统中，以促进内体逃逸。在这篇综述中，已经详细讨论了不同类型NP的内体逃逸机制，并将其与病毒和其他合成基因传递系统从内体逃逸的内体逃逸机制进行了比较。而且，探索了基于不同方法和策略的内溶体药物的设计以促进内体逃逸。而且，