Gomerdinger Victoria F, Nabar Namita, Hammond Paula T
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nat Rev Cancer. 2025 Aug 1. doi: 10.1038/s41568-025-00847-2.
Engineered nanoparticles have greatly expanded cancer treatment by encapsulating and delivering therapeutic and diagnostic agents, otherwise limited by poor pharmacokinetics and toxicity, to target tumour cells. Leveraging our increased understanding of the tumour microenvironment, nanomedicine has expanded to additionally target key tissues and cells implicated in tumorigenesis, such as immune and stromal cells, to improve potency and further mitigate off-target toxicities. To design nanocarriers that overcome the body's physiological barriers to access tumours, the field has explored broader routes of administration and nanoparticle design principles, beyond the enhanced permeation and retention effect. This Review explores the advantages of non-covalent surface modifications of nanoparticles, along with other surface modifications, to modulate nanoparticle trafficking from the injection site, into tumour and lymphoid tissues, to the target cell, and ultimately its subcellular fate. Using electrostatic or other non-covalent techniques, nanoparticle surfaces can be decorated with native and synthetic macromolecules that confer highly precise cell and tissue trafficking. Rational design can additionally minimize detection and clearance by the immune system and prolong half-life - key to maximizing efficacy of therapeutic cargos. Finally, we outline how cancer nanomedicine continues to evolve by incorporating learnings from novel screening technologies, computational approaches and patient-level data to design efficacious targeted therapies.
工程纳米颗粒通过包裹和递送治疗与诊断药物极大地扩展了癌症治疗手段，否则这些药物会因药代动力学不佳和毒性问题而受到限制，从而靶向肿瘤细胞。借助我们对肿瘤微环境的深入了解，纳米医学已扩展到额外靶向参与肿瘤发生的关键组织和细胞，如免疫细胞和基质细胞，以提高疗效并进一步减轻脱靶毒性。为了设计能够克服身体生理屏障以进入肿瘤的纳米载体，该领域已探索了除增强渗透和滞留效应之外更广泛的给药途径和纳米颗粒设计原则。本综述探讨了纳米颗粒非共价表面修饰以及其他表面修饰的优势，以调节纳米颗粒从注射部位到肿瘤和淋巴组织再到靶细胞的转运，最终确定其亚细胞命运。使用静电或其他非共价技术，纳米颗粒表面可以用天然和合成大分子进行修饰，从而实现高度精确的细胞和组织转运。合理设计还可以最大限度地减少免疫系统的检测和清除，并延长半衰期——这是使治疗药物疗效最大化的关键。最后，我们概述了癌症纳米医学如何通过纳入来自新型筛选技术、计算方法和患者层面数据的知识来持续发展，以设计有效的靶向疗法。
