Xu Zhenyu, Liu Siyan, Li Yanan, Wu Yanping, Tu Jiasheng, Chen Qian, Sun Chunmeng
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China.
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Acta Pharm Sin B. 2025 Aug;15(8):3951-3977. doi: 10.1016/j.apsb.2025.05.039. Epub 2025 Jun 6.
Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.
在过去几十年中，肿瘤免疫疗法彻底改变了癌症临床治疗的格局。为提高单一免疫疗法的抗肿瘤疗效，联合策略蓬勃发展。然而，与其简单地将多种治疗方法组合，不如通过设计合理的组合及给药策略来追求协同效应，这基于对生理和病理特征的全面理解。在这种情况下，联合药物的给药时间和空间分布成为实现更好治疗效果的关键因素。因此，提出了序贯给药系统（SDDS）的概念，通过内部条件触发和/或外部干预来定义时空编程的药物递送/释放，从而顺应动态的疾病演变和人体免疫。本文综述了用于时空调节联合肿瘤免疫治疗的基于生物材料的SDDS的最新进展。此外，还讨论了各种工程策略背后的原理。最后，概述了潜在的协同机制及其在联合免疫治疗中的前景。
