State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P. R. China.
Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry, Ministry of Education, Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin 300387, P. R. China.
ACS Appl Mater Interfaces. 2021 Nov 17;13(45):53564-53573. doi: 10.1021/acsami.1c14385. Epub 2021 Nov 2.
Intelligent drug delivery systems (DDSs) that can improve therapeutic outcomes of antitumor agents and decrease their side effects are urgently needed to satisfy special requirements of treatment of malignant tumors in clinics. Here, the fabrication of supramolecular self-assembled amphiphiles based on the host-guest recognition between a cationic water-soluble pillar[6]arene (WP6A) host and a sodium decanesulfonate guest (G) is reported. The chemotherapeutic agent doxorubicin hydrochloride (DOX) can be encapsulated into the formed vesicle (G/WP6A) to construct supramolecular DDS (DOX@G/WP6A). WP6A affords strong affinities to G to avoid undesirable off-target leakage during delivery. Nanoscaled DOX@G/WP6A is capable of preferentially accumulating in tumor tissue via enhanced permeability and retention (EPR) effect. After internalization by tumor cells, the abundant adenosine triphosphate (ATP) binds competitively with WP6A to trigger the disintegration of self-assembled vesicles with the ensuing release of DOX. and research confirmed that DOX@G/WP6A is not only able to promote antitumor efficacy but also reduce DOX-related systemic toxicity. The above favorable findings are ascribed to the formation of ternary self-assembly, which profits from the combination of the factors of the EPR effect and the ATP-triggered release.
智能药物输送系统 (DDS) 能够提高抗肿瘤药物的治疗效果，降低其副作用，这是满足临床恶性肿瘤治疗特殊要求的迫切需要。在这里，报道了基于阳离子水溶性柱[6]芳烃 (WP6A) 主体与十二烷磺酸钠客体 (G) 之间主客体识别的超分子自组装两亲物的制备。化疗药物盐酸多柔比星 (DOX) 可以被包裹到形成的囊泡 (G/WP6A) 中，构建超分子 DDS (DOX@G/WP6A)。WP6A 与 G 具有很强的亲和力，以避免在输送过程中出现不理想的脱靶泄漏。纳米级 DOX@G/WP6A 能够通过增强渗透和保留 (EPR) 效应优先积聚在肿瘤组织中。在被肿瘤细胞内化后，大量的三磷酸腺苷 (ATP) 与 WP6A 竞争结合，触发自组装囊泡的解体，随之释放 DOX。 和 研究证实，DOX@G/WP6A 不仅能够提高抗肿瘤疗效，还能降低 DOX 相关的全身毒性。上述有利发现归因于三元自组装的形成，这得益于 EPR 效应和 ATP 触发释放因素的结合。
