期刊
ACS APPLIED MATERIALS & INTERFACES
卷 10, 期 23, 页码 19347-19354出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b01869
关键词
hierarchical assembly; gene delivery; siRNA; cell internalization; nanomedicine; fullerene
资金
- KAKENHI [15H05754, 17H03036]
- Japan Agency for Science and Technology (CREST) [JPMJCR14L4]
- Japan Society for the Promotion of Science
Delivery of siRNA is a key technique in alternative gene therapy, where the siRNA cargo must be effectively loaded onto a tailor-designed carrier molecule and smoothly unloaded precisely upon arrival at the target cells or organs. Any toxicity issues also need to be mitigated by suitable choice of the carrier molecule. A water-soluble cationic fullerene, tetra(piperazino)[60]fullerene epoxide (TPFE), was previously shown to be nontoxic and effective for lung-targeted in vivo siRNA delivery by way of agglutination-induced accumulation. We found in this in vitro study that hierarchical reversible assembly of micrometer-sized TPFE-siRNA-serum protein ternary complexes is the key element for effective loading and release, and stabilization of otherwise highly unstable siRNA under the physiological conditions. The amphiphilic TPFE molecule forms a sub-10 nm-sized stable micelle because of strong cohesion between fullerene molecules, and this fullerene aggregate protects siRNA and induces the hierarchical assembly. Unlike popularly used polyamine carriers, TPFE is not toxic at the dose used for the siRNA delivery.
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