A novel biomimetic nanovesicle-loaded supramolecular enzyme-based therapeutics has been developed. Here, using a biomimetic lipid-D-α-tocopherol polyethylene glycol succinate (TPGS) hybrid semi-permeable membrane, cyclodextrin supramolecular docking, metal-ion-aided coordination complexing, we combined multiple functional motifs into a single biomimetic microbioreactor-supramolecular nanovesicle (MiSuNv) that allowed effective transport of arginine deiminase (ADI) to hepatic tumor cells to enhance arginine depletion. We compared two intercalated enzyme-carrying supermolecular motifs mainly comprising of 2-hydroxypropyl-β-cyclodextrin and sulfobutyl-ether-β-cyclodextrin, the only two cyclodextrin derivatives approved for injection by the United States Food and Drug Administration. The ADI-specific antitumor effects were enhanced by TPGS (one constituent of MiSuNv, having synergistic antitumor effects), as ADI was separated from adverse external environment by a semi-permeable membrane and sequestered in a favorable internal microenvironment with an optimal pH and metal-ion combination. ADI@MiSuNv contributed to cell cycle arrest, apoptosis and autophagy through the enhanced efficacy of enzyme treatment against Hep3B xenograft tumors in rats.

一种新型仿生纳米囊泡负载超分子酶疗法已被开发出来。在这里，我们使用仿生脂质-D-α-生育酚聚乙二醇琥珀酸酯（TPGS）混合半透膜、环糊精超分子对接、金属离子辅助配位络合，将多个功能基序组合成一个仿生微生物反应器-超分子纳米囊泡（ MiSuNv) 允许将精氨酸脱亚胺酶 (ADI) 有效转运至肝肿瘤细胞以增强精氨酸消耗。我们比较了两种嵌入的携带酶的超分子基序，主要由 2-羟丙基-β-环糊精和磺丁基-醚-β-环糊精组成，这是美国食品和药物管理局批准用于注射的仅有的两种环糊精衍生物。TPGS（MiSuNv 的一种成分，具有协同抗肿瘤作用）增强了 ADI 特异性抗肿瘤作用，因为 ADI 通过半透膜与不利的外部环境隔离，并隔离在具有最佳 pH 值和金属的有利内部微环境中。离子组合。ADI@MiSuNv 通过增强酶治疗对大鼠 Hep3B 异种移植肿瘤的疗效，促进细胞周期停滞、细胞凋亡和自噬。