A ternary core/shell based nanoparticulate complex was designed for the sequential and site-specific drug delivery. First, bovine serum albumin nanoparticles (BSA NPs) were served as the core for loading gambogic acid (GA). Subsequently, the BSA NPs were adsorbed by polyethylenimine and then shielded with carboxymethyl chitosan-folate (CMCS-FA) as the outer shell for encapsulating tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), forming the GA/TRAIL co-delivery BSA (GTB) NPs. In normal tissues, the GTB NPs were negatively charged; in acidic tumor tissues, the shielding CMCS-FA was detached, allowing the release of TRAIL, which binds to the cell death receptor on the plasma membrane. The resulting positively charged complex promoted cellular internalization and escaped from lysosomes, producing a rapid release of GA, which exerted the combined tumor therapy by regulating both intrinsic and extrinsic apoptotic pathways. In vitro and in vivo studies confirmed that GTB NPs could enhance antitumor efficacy and reduce adverse effects.

设计了基于三元核/壳的纳米微粒复合物，用于顺序和特定位置的药物输送。首先，牛血清白蛋白纳米颗粒（BSA NPs）被用作装载藤黄酸（GA）的核心。随后，BSA NPs被聚乙烯亚胺吸附，然后用羧甲基壳聚糖-叶酸（CMCS-FA）作为外壳进行包封，以封装肿瘤坏死因子相关的凋亡诱导配体（TRAIL），形成GA / TRAIL共递送BSA （GTB）NP。在正常组织中，GTB NPs带负电；在酸性肿瘤组织中，屏蔽性CMCS-FA被分离，从而释放TRAIL，该TRAIL与质膜上的细胞死亡受体结合。产生的带正电荷的复合物促进细胞内化并从溶酶体中逃逸，从而产生GA的快速释放，通过调节内在和外在的凋亡途径发挥了联合肿瘤治疗的作用。体外和体内研究证实，GTB NP可以增强抗肿瘤功效并减少不良反应。