Here we describe two protocols for the construction of responsive and activable nanomedicines that regulate the tumor microenvironment (TME). The TME is composed of all non-cellular and cellular components surrounding a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules, and extracellular matrix and has a crucial role in tumor initiation, growth, and metastasis. Owing to the relatively stable properties of the TME compared to tumor cells, which exhibit frequent genetic mutations and epigenetic changes, therapeutic strategies targeting the TME using multifunctional nanomedicines hold great potential for anti-tumor therapy. By regulating tumor-associated platelets and pancreatic stellate cells (PSCs), the two major players in the TME, we can effectively manipulate the physiological barriers for enhanced drug delivery and significantly improve the tumor penetration and therapeutic efficacy of chemotherapeutics. The preparation and characterization of the multifunctional nanoparticles takes ~10 h for tumor-associated platelet regulation and 16 h for PSC regulation. These nanoformulations can be readily applied to regulate other components in the TME to realize synergistic or additive anti-tumor activity.

在这里，我们描述了两种用于构建调节肿瘤微环境 (TME) 的响应性和可激活纳米药物的协议。TME由肿瘤周围的所有非细胞和细胞成分组成，包括周围的血管、免疫细胞、成纤维细胞、信号分子和细胞外基质，在肿瘤的起始、生长和转移中起着至关重要的作用。由于 TME 与肿瘤细胞相比具有相对稳定的特性，肿瘤细胞表现出频繁的基因突变和表观遗传变化，因此使用多功能纳米药物靶向 TME 的治疗策略在抗肿瘤治疗方面具有巨大潜力。通过调节肿瘤相关血小板和胰腺星状细胞 (PSCs) 这两个 TME 的主要参与者，我们可以有效地操纵生理屏障以增强药物输送，并显着提高化疗药物的肿瘤穿透性和治疗效果。多功能纳米粒子的制备和表征需要约 10 小时用于肿瘤相关的血小板调节和 16 小时用于 PSC 调节。这些纳米制剂可以很容易地用于调节 TME 中的其他成分，以实现协同或相加的抗肿瘤活性。