Key Laboratory of Functional Polymer Materials of the Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
J Mater Chem B. 2020 May 14;8(18):3959-3971. doi: 10.1039/d0tb00289e.
Over the past decade, nanoparticle-based drug delivery systems have been extensively explored. However, the average tumour enrichment ratio of passive targeting systems corresponds to only 0.7% due to the nonspecific uptake by normal organs and poor selective retention in tumours. The therapeutic specificity and efficacy of nano-medicine can be enhanced by equipping it with active targeting ligands, although it is not possible to ignore the recognition and clearance of the reticuloendothelial system (RES) caused by targeting ligands. Given the complexity of the systemic circulation environment, it is necessary to carefully consider the hydrophobicity, immunogenicity, and electrical property of targeting ligands. Thus, for an active targeting system, the targeting ligands should be shielded in blood circulation and de-shielded in the tumour region for enhanced tumour accumulation. In this study, strategies for improving the performance of active targeting ligands are introduced. The strategies include irreversible shielding, reversible shielding, and methods of modulating the multivalent interactions between ligands and receptors. Furthermore, challenges and future developments in designing active ligand targeting systems are also discussed.
在过去的十年中，基于纳米粒子的药物传递系统得到了广泛的研究。然而，由于正常器官的非特异性摄取和肿瘤中缺乏选择性滞留，被动靶向系统的平均肿瘤富集率仅为 0.7%。通过给纳米药物配备主动靶向配体，可以提高其治疗的特异性和疗效，尽管不能忽视靶向配体引起的网状内皮系统（RES）的识别和清除。考虑到系统循环环境的复杂性，有必要仔细考虑靶向配体的疏水性、免疫原性和电性。因此，对于主动靶向系统，靶向配体应该在血液循环中被屏蔽，并在肿瘤区域被去屏蔽，以增强肿瘤的积累。本研究介绍了提高主动靶向配体性能的策略。这些策略包括不可逆屏蔽、可逆屏蔽以及调节配体和受体之间多价相互作用的方法。此外，还讨论了设计主动配体靶向系统的挑战和未来发展。
