Cancer represents a significant threat to human health. The cells and tissues within the microenvironment of solid tumors exhibit complex and abnormal properties in comparison to healthy tissues. The efficacy of nanomedicines is inhibited by the presence of substantial and complex physical barriers in the tumor tissue. The latest generation of intelligent drug delivery systems, particularly nanomedicines capable of charge reversal, have shown promise in addressing this issue. These systems can transform their charge from negative to positive upon reaching the tumor site, thereby enhancing tumor penetration via transcytosis and promoting cell internalization by interacting with the negatively charged cell membranes. The modification of nanocarriers with 2,3-dimethylmaleic anhydride (DMMA) and its derivatives, which are responsive to weak acid stimulation, represents a significant advance in the field of charge-reversal nanomedicines. This review provides a comprehensive examination of the recent insights into DMMA-modified nanocarriers in drug delivery systems, with a particular focus on their potential in targeted therapeutics. It also discusses the synthesis of DMMA derivatives and their role in charge reversal, shell detachment, size shift, and ligand reactivation mechanisms, offering the prospect of a tailored, next-generation therapeutic approach to overcome the diverse challenges associated with cancer therapy.

中文翻译：

---

药物输送系统中 2,3-二甲基马来酸酐 (DMMA) 修饰的纳米载体的进展


癌症对人类健康构成重大威胁。与健康组织相比，实体瘤微环境中的细胞和组织表现出复杂且异常的特性。纳米药物的功效因肿瘤组织中存在大量且复杂的物理屏障而受到抑制。最新一代的智能药物输送系统，特别是能够反转电荷的纳米药物，在解决这个问题方面显示出了希望。这些系统在到达肿瘤部位后可以将其电荷从负电转变为正电，从而通过转胞吞作用增强肿瘤渗透，并通过与带负电的细胞膜相互作用促进细胞内化。用2,3-二甲基马来酸酐（DMMA）及其衍生物对纳米载体进行修饰，对弱酸刺激有响应，代表了电荷反转纳米医学领域的重大进展。本综述对药物输送系统中 DMMA 修饰的纳米载体的最新见解进行了全面审查，特别关注其在靶向治疗中的潜力。它还讨论了 DMMA 衍生物的合成及其在电荷反转、壳分离、尺寸变化和配体再激活机制中的作用，为定制的下一代治疗方法克服与癌症治疗相关的各种挑战提供了前景。