College of Pharmacy, Dongduk Women's University, Seoul, 02748, Republic of Korea.
Department of Medical Life Sciences and Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Arch Pharm Res. 2023 Jan;46(1):18-34. doi: 10.1007/s12272-022-01425-y. Epub 2023 Jan 3.
Biological cell membranes are a natural barrier for living cells. In the last few decades, the cell membrane has been the main hurdle in the efficient delivery of bioactive and therapeutic agents. To increase the drug efficacy of these agents, additional mediators have been considered. Cell-penetrating peptides (CPPs), a series of oligopeptides composed of mostly hydrophobic and/or positively charged side chains, can increase the interaction with the cell membrane. CPP-based delivery platforms have shown great potential for the efficient and direct cytosol delivery of various cargos, including genes, proteins, and small molecule drugs. Bypassing endocytosis allows the CPP-based delivery systems greater defense against the degradation of protein-based drugs than other drug delivery systems. However, the delivery of CPPs exhibits intrinsically non-specific targeting, which limits their medical applications. To endow CPPs with specific targeting ability, the conjugation of pH-sensitive, enzyme-specific cleavable, and multiple targeting ligands has been reported. Optimization of the length and sequence of CPPs is still needed for various drugs of different sizes and surface charges. Toxicity issues in CPP-based delivery systems should be addressed carefully before clinical use.
生物细胞膜是活细胞的天然屏障。在过去的几十年中，细胞膜一直是生物活性和治疗剂有效传递的主要障碍。为了提高这些药物的疗效，人们考虑了其他的介导物。细胞穿透肽（CPPs）是由大多数疏水性和/或带正电荷的侧链组成的一系列寡肽，可以增加与细胞膜的相互作用。基于 CPP 的递药平台在有效和直接将各种载药（包括基因、蛋白质和小分子药物）递送到细胞质方面显示出巨大的潜力。绕过内吞作用使基于 CPP 的递药系统比其他递药系统具有更大的防御能力来抵抗基于蛋白质的药物的降解。然而，CPP 的递药表现出固有非特异性靶向性，这限制了它们的医学应用。为了赋予 CPP 特定的靶向能力，已经报道了 pH 敏感、酶特异性可切割和多靶向配体的缀合。对于不同大小和表面电荷的各种药物，还需要优化 CPP 的长度和序列。在临床应用之前，应仔细解决基于 CPP 的递药系统的毒性问题。
