文章：

推进靶向癌症纳米药物的工程设计策略

Advancing engineering design strategies for targeted cancer nanomedicine

原文发布日期：2025-08-01

DOI: 10.1038/s41568-025-00847-2

类型: Review Article

开放获取: 否

英文摘要：

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.

摘要翻译： 

工程纳米粒子通过封装和递送治疗及诊断剂，极大地扩展了癌症治疗手段，这些剂型原本因药代动力学特性不佳和毒性问题而受限。随着对肿瘤微环境认识的深入，纳米医学已进一步靶向涉及肿瘤发生的关键组织和细胞（如免疫细胞和基质细胞），以提升疗效并减少脱靶毒性。为了设计能够克服机体生理屏障并抵达肿瘤的纳米载体，该领域探索了更广泛的给药途径和纳米粒子设计原则，超越了增强渗透和滞留效应的范畴。本综述探讨了纳米粒子非共价表面修饰及其他表面修饰策略的优势，以调控纳米粒子从注射部位到肿瘤及淋巴组织、再到靶细胞，并最终决定其亚细胞命运的运输过程。通过静电或其他非共价技术，纳米粒子表面可修饰天然或合成大分子，从而实现高度精准的细胞和组织运输。合理设计还能最大限度地减少免疫系统的检测和清除，延长半衰期——这是最大化治疗载荷功效的关键。最后，我们概述了癌症纳米医学如何通过整合新型筛选技术、计算方法及患者层面数据的洞见，持续演进以设计高效靶向疗法。

原文链接：

Advancing engineering design strategies for targeted cancer nanomedicine