期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 45, 页码 53564-53573出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c14385
关键词
drug delivery system; host-guest recognition; self-assembled amphiphile; competitive release; chemotherapy
资金
- Natural Science Foundation of Beijing Municipality [7204285]
- National Natural Science Foundation of China [21772118, 21971192, 81573354]
- Natural Science Foundation of Tianjin City [20JCZDJC00200]
This study introduces an intelligent drug delivery system based on supramolecular self-assembled amphiphiles, which encapsulates and releases chemotherapeutic agents through host-guest recognition, leading to enhanced antitumor efficacy and reduced systemic toxicity. The system achieves preferential accumulation and release in tumor tissue by utilizing the EPR effect and ATP-triggered release mechanism.
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. In vitro and in vivo 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.
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