Capping Silica Nanoparticles with Tryptophan‐Mediated Cucurbit[8]uril Complex for Targeted Intracellular Drug Delivery Triggered by Tumor‐Overexpressed IDO1 Enzyme
Capping Silica Nanoparticles with Tryptophan‐Mediated Cucurbit[8]uril Complex for Targeted Intracellular Drug Delivery Triggered by Tumor‐Overexpressed IDO1 Enzyme
复制标题
DOI：
10.1002/adhm.201900174
复制
发表时间：
2019-04
影响因子：
10
通讯作者：
Haishi Qiao;Jing Jia;Haowen Shen;Si-jia Zhao;E. Chen;Wei Chen;Bin Di;Chi Hu
中科院分区：
文献类型：
--
作者：
Haishi Qiao;Jing Jia;Haowen Shen;Si-jia Zhao;E. Chen;Wei Chen;Bin Di;Chi Hu
对肿瘤特异性酶敏感的纳米系统被认为是一种极具吸引力的细胞内药物释放方法，用于靶向癌症治疗。介孔二氧化硅纳米颗粒被色氨酸介导的葫芦[8]脲与 Fe3O4 复合物覆盖，以最大程度地减少药物过早泄漏，同时能够根据需要将有效负载输送到目标组织。色氨酸和葫芦[8]脲之间的超分子相互作用在吲哚胺 2,3-双加氧酶 1 (IDO1) 酶（肿瘤细胞内微环境中丰富）的存在下被破坏，该酶催化色氨酸代谢为 N-甲酰犬尿氨酸，导致纳米载体的“看门人”分解，并仅在肿瘤细胞中释放治疗药物。纳米载体对过表达的IDO1酶具有高选择性地释放药物，在体外对HepG2细胞产生显着的细胞毒性，在体内也具有优异的抗肿瘤作用。这种具有复杂结构和特性的强大超分子纳米系统为针对肿瘤细胞内固有微环境酶的细胞内药物释放提供了一个有前景的平台。
Nanosystems responsive to tumor‐specific enzymes are considered as a highly attractive approach to intracellular drug release for targeted cancer therapy. Mesoporous silica nanoparticles are capped with tryptophan‐mediated cucurbit[8]uril complex with Fe3O4 to minimize the premature drug leakage while being able to deliver the payload on demand at the target tissue. The supramolecular interaction between tryptophan and cucurbit[8]uril is disrupted in the presence of indoleamine 2,3‐dioxygenase 1 (IDO1) enzyme (abundant in the tumor intracellular microenvironment), which catalyzes the metabolism of tryptophan into N‐formylkynurenine, resulting in the disassembly of the “gate‐keeper” of the nanocarriers and intracellular release of therapeutics exclusively in tumor cells. The drug release from the nanocarrier with high selectivity to overexpressed IDO1 enzyme induces significant cytotoxicity against HepG2 cells in vitro, as well as the superior antitumor effects in vivo. This robust supramolecular nanosystem with sophisticated structure and property provides a promising platform for intracellular drug release targeting the intrinsic microenvironmental enzyme inside the tumor cells.