Prodrugs containing lipid moieties attached to drug derivatives, such as anti-cancer drug derivatives, via linkers comprising disulfide groups are described. Also described are nanoparticles coated with a lipid layer containing the prodrugs, formulations comprising the nanoparticles, and the use of the nanoparticles in methods of treating diseases, such as cancer, alone or in combination with additional drug compounds, targeting agents, and/or immunotherapy agents, such as immunosuppression inhibitors that target the CTLA-4, PD-1/PD-L1, IDO, LAG-3, CCR-7 or other pathways, or multiple immunosuppression inhibitors targeting a combination of such pathways. Optionally, the nanoparticles can comprise a photosensitizer or a derivative thereof and can be used in methods involving photodynamic therapy. Synergistic therapeutic effects result from combinations of multiple modalities provided by the disclosed nanoparticles and/or nanoparticle formulations.
本文描述了含有脂质分子的原药,这些脂质分子通过包含二
硫基团的连接体连接到药物衍
生物(如抗癌药物衍
生物)上。还描述了涂有包含原药的脂质层的纳米颗粒、包含纳米颗粒的制剂,以及纳米颗粒在治疗疾病(如癌症)的方法中的用途,单独使用或与其他药物化合物、靶向制剂和/或免疫疗法制剂(如靶向 CT
LA-4、PD-1/PD-L1、
IDO、
LAG-3、CCR-7 或其他途径的免疫抑制
抑制剂,或靶向此类途径组合的多种免疫抑制
抑制剂)组合使用。可选地,纳米颗粒可包含光敏剂或其衍
生物,并可用于涉及光动力疗法的方法中。所公开的纳米颗粒和/或纳米颗粒制剂提供的多种方式的组合可产生协同治疗效果。