期刊
BIOMATERIALS
卷 185, 期 -, 页码 205-218出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.09.016
关键词
HDL nanostructures; AS1411 aptamer; CpG motif; Relay drug delivery; Amplify chemo-immunotherapy
资金
- National Natural Science Foundation of China [81501582, 81573379, 81601594, 81872819]
- Natural Science Foundation of Jiangsu Province [BK20171390]
- National Key Research and Development Program [2017YFD0501403]
- National Science and Technology Major Project [2017ZX09101001]
- Development Funds for Priority Academic Programs in Jiangsu Higher Education Institutions
- Fostering Plan of University Scientific and Technology Innovation Team of Jiangsu Qing Lan Project
Chemo-immunotherapy represents an appealing approach to improving cancer treatment. Simultaneously administrating chemotherapeutics with immunoadjuvants can elicit potent tumor death and immune responses. Herein, high density lipoprotein (HDL) inspired immune lipoprotein was proposed for relay drug delivery and amplifying antitumor therapy. Lipophilic AS1411 aptamer-immunoadjuvant CpG fused sequences (Apt-CpG-DSPE) were conjugated to facilitate decoration onto HDLs; and doxorubicin (Dox) was successively intercalated into the consecutive base pairs of Apt-CpG to complete immune HDL nanodrug imHDL/Apt-CpG-Dox. For relay drug delivery, imHDL/Apt-CpG-Dox underwent site-specific structure collapse in tumor intercellular substances inspired from HDL biofunctions (sequential module I); subsequently, dissociated Apt-CpG-Dox was endocytosed into tumor cells mediated by the recognition of AS1411 and nucleolin (sequential module II), translocating Dox to nucleus and enabling tumor ablation and antigens release. The liberated CpG motif further evoked antigen recognition, induced vast secretion of pro-inflammatory cytokines and potentiated host antitumor immunity. Our studies demonstrated that HDL biomimetic platform based relay drug delivery strategy outperformed the monotherapy counterparts in malignant tumor models, eventually generating an augmented antitumor efficacy.
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