Department of Polymeric Materials, School of Materials Science and Engineering, Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education, Tongji University, 4800 Caoan Road, Shanghai 201804, People's Republic of China.
Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, People's Republic of China.
Biomed Mater. 2021 May 24;16(4). doi: 10.1088/1748-605X/abffb5.
Nanocarriers (NCs) for delivery anticancer therapeutics have been under development for decades. Although great progress has been achieved, the clinic translation is still in the infancy. The key challenge lies in the biological barriers which lie between the NCs and the target spots, including blood circulation, tumor penetration, cellular uptake, endo-/lysosomal escape, intracellular therapeutics release and organelle targeting. Each barrier has its own distinctive microenvironment and requires different surface charge. To address this challenge, charge-reversal polymeric NCs have been a hot topic, which are capable of overcoming each delivery barrier, by reversing their charges in response to certain biological stimuli in the tumor microenvironment. In this review, the triggering mechanisms of charge reversal, including pH, enzyme and redox approaches are summarized. Then the corresponding design principles of charge-reversal NCs for each delivery barrier are discussed. More importantly, the limitations and future prospects of charge-reversal NCs in clinical applications are proposed.
纳米载体（NCs）用于递抗癌治疗药物已经开发了几十年。尽管已经取得了很大的进展，但临床转化仍处于起步阶段。关键挑战在于 NCs 与靶标之间的生物学屏障，包括血液循环、肿瘤渗透、细胞摄取、内体/溶酶体逃逸、细胞内治疗药物释放和细胞器靶向。每个屏障都有其独特的微环境，需要不同的表面电荷。为了解决这个挑战，电荷反转聚合物 NCs 一直是一个热门话题，它们能够克服每个递药障碍，通过在肿瘤微环境中响应某些生物刺激来反转它们的电荷。在这篇综述中，总结了电荷反转的触发机制，包括 pH、酶和氧化还原方法。然后讨论了针对每个递药障碍的电荷反转 NCs 的相应设计原则。更重要的是，提出了电荷反转 NCs 在临床应用中的局限性和未来前景。
