pH响应型药物递送系统在肿瘤免疫治疗领域的研究进展

Research progress of pH-responsive drug delivery systems in cancer immunotherapy

肿瘤免疫疗法是激活宿主自身免疫系统对抗肿瘤的治疗方式,已广泛应用于临床,然而存在响应率低、免疫相关不良事件等缺陷。有别于传统的化学治疗,免疫治疗的靶标表现出更为广泛的空间异质性,分布在不同细胞类型及二级细胞器中,药物分子易产生脱靶与在靶毒性,极大地影响了治疗的有效性与安全性。由于代谢水平的改变,肿瘤微环境较正常组织显微酸性,而细胞内吞途径伴随着质子的进一步泵入,因此pH可以作为理想的选择性刺激条件,以实现“门控”式的药物精准递释。近年来,pH响应型材料在肿瘤免疫治疗中被广泛研究,如高分子聚合物、生物大分子、脂质纳米粒、生物膜、无机纳米粒、金属-有机框架等。本文从不同的载体类型出发,综述了pH响应型肿瘤免疫治疗的研究策略,为新一代靶向制剂研发提供参考。

Cancer immunotherapy,which is an attractive strategy harnessing the host's own immune system to remove tumor cells,has been widely used in clinical practice,yet with low response rate and immune-related adverse events.Unlike traditional chemotherapy,the targets of immunotherapy exhibit high spatial heterogeneity and are distributed in different cell types or secondary organelles,resulting in off-target and on-target toxicity,which greatly reduces the efficacy and safety of treatment.Due to the altered metabolic level,tumor tissues often display a lower pH than normal tissues.In addition,the endocytosis pathway is accompanied by continuous pumping of protons.Therefore,the variation of environmental pH values could serve as an ideal stimulus for precise drug delivery and release.In recent years,pH-responsive materials(e.g.,polymers,biomacromolecules,lipid nanoparticles,biofilm,inorganic nanoparticles,and metal-organic frameworks)have been widely investigated in the field of cancer immunotherapy.This paper summarizes recent strategies of pH-responsive drug delivery systems based on different types of carriers,aiming to provide some reference for the design of next generation of tumor-targeting formulations in cancer immunotherapy.