微载体是一种有前途的药物输送系统，在治疗癌症方面显示出重要的价值。主要目标之一是设计具有巧妙结构和功能的微载体，以实现更好的肿瘤治疗效果。在这里，受细胞核-细胞质结构及其之间的物质交换反应的启发，我们从微流控技术中开发出一种双正交隔室微粒（BCM），可以分别加载和顺序释放环辛烯修饰的阿霉素前药（TCO-DOX）和用于肿瘤治疗的四嗪修饰吲哚菁绿（Tz-ICG）。 Tz-ICG 不仅可以作为 TCO-DOX 的激活剂，还可以作为光热剂，允许生物正交化疗和光热疗法 (PTT) 的结合。此外，环辛烯对DOX的修饰显着降低了DOX的全身毒性。因此，所开发的 BCM 表现出有效的体外肿瘤细胞根除作用，并表现出显着的肿瘤生长抑制作用，且安全性良好。这些发现表明，配制的 BCM 建立了一个生物正交前药激活和局部递送的平台，在癌症治疗和相关应用中具有巨大潜力。© 2024。作者。

Microcarrier is a promising drug delivery system demonstrating significant value in treating cancers. One of the main goals is to devise microcarriers with ingenious structures and functions to achieve better therapeutic efficacy in tumors. Here, inspired by the nucleus-cytoplasm structure of cells and the material exchange reaction between them, we develop a type of biorthogonal compartmental microparticles (BCMs) from microfluidics that can separately load and sequentially release cyclooctene-modified doxorubicin prodrug (TCO-DOX) and tetrazine-modified indocyanine green (Tz-ICG) for tumor therapy. The Tz-ICG works not only as an activator for TCO-DOX but also as a photothermal agent, allowing for the combination of bioorthogonal chemotherapy and photothermal therapy (PTT). Besides, the modification of DOX with cyclooctene significantly decreases the systemic toxicity of DOX. As a result, the developed BCMs demonstrate efficient in vitro tumor cell eradication and exhibit notable tumor growth inhibition with favorable safety. These findings illustrate that the formulated BCMs establish a platform for bioorthogonal prodrug activation and localized delivery, holding significant potential for cancer therapy and related applications.© 2024. The Author(s).