由于抗胃癌药物的非靶向释放和溶解度低，一线药物阿帕替尼（Apa）长期大剂量使用往往会诱发多重耐药，产生严重的副作用。为了避免这些缺点，采用透明质酸（HA）修饰的脂质膜包覆的普鲁士蓝纳米颗粒（PB NPs）用于Apa负载，以提高其溶解度和靶向能力。此外，选择抗肿瘤化合物伽布福林（CS-6）作为Apa的搭档，减少胃联合治疗的剂量。因此，构建了HA-Apa-Lip@PB-CS-6 NPs以将两种药物同步转运到肿瘤组织中。体外实验表明，HA-Apa-Lip@PB-CS-6 NPs 可通过下调血管内皮生长因子受体 (VEGFR) 和基质金属蛋白酶-9 (MMP-9) 协同抑制 BGC-823 细胞的增殖和侵袭/转移。体内实验表明，与其他组相比，HA-Apa-Lip@PB-CS-6 NPs 在 BGC-823 细胞荷载小鼠中的给药具有最强的抗肿瘤生长和肝转移作用，因为它在肿瘤组织中具有出色的渗透性和突出的协同效应。总之，我们成功开发了一种用于同步 Apa/CS-6 递送和协同胃癌 (GC) 治疗的新型纳米复合物。© 2023 作者。

Due to the non-targeted release and low solubility of anti-gastric cancer agent, apatinib (Apa), a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects. In order to avoid these drawbacks, lipid-film-coated Prussian blue nanoparticles (PB NPs) with hyaluronan (HA) modification was used for Apa loading to improve its solubility and targeting ability. Furthermore, anti-tumor compound of gamabufotalin (CS-6) was selected as a partner of Apa with reducing dosage for combinational gastric therapy. Thus, HA-Apa-Lip@PB-CS-6 NPs were constructed to synchronously transport the two drugs into tumor tissue. In vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase-9 (MMP-9). In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs administration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects. In summary, we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer (GC) therapy.© 2023 The Authors.