TY - JOUR
T1 - Hierarchical Assembly of siRNA with Tetraamino Fullerene in Physiological Conditions for Efficient Internalization into Cells and Knockdown
AU - Minami, Kosuke
AU - Okamoto, Koji
AU - Harano, Koji
AU - Noiri, Eisei
AU - Nakamura, Eiichi
N1 - Funding Information:
We thank M. Ohta (Shimadzu Co.), S. Moriguchi (Shimadzu AMC, Inc.), and A. Kogure (Shimadzu AMC, Inc.) for AFM measurement using the Shimadzu Co., Modified SPM-9700. This study was financially supported by KAKENHI (No. 15H05754 to E. Nakamura and E. Noiri and No. 17H03036 to K.H.), and the Japan Agency for Science and Technology (CREST; JPMJCR14L4 to E. Nakamura). K.M. thanks the Japan Society for the Promotion of Science for a predoctoral fellowship.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/6/13
Y1 - 2018/6/13
N2 - 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.
AB - 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.
KW - cell internalization
KW - fullerene
KW - gene delivery
KW - hierarchical assembly
KW - nanomedicine
KW - siRNA
UR - http://www.scopus.com/inward/record.url?scp=85046965870&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046965870&partnerID=8YFLogxK
U2 - 10.1021/acsami.8b01869
DO - 10.1021/acsami.8b01869
M3 - Article
C2 - 29742343
AN - SCOPUS:85046965870
VL - 10
SP - 19347
EP - 19354
JO - ACS applied materials & interfaces
JF - ACS applied materials & interfaces
SN - 1944-8244
IS - 23
ER -