Self-Assembly of siRNA/PEG- b-Catiomer at Integer Molar Ratio into 100 nm-Sized Vesicular Polyion Complexes (siRNAsomes) for RNAi and Codelivery of Cargo Macromolecules

Beob Soo Kim, Sayan Chuanoi, Tomoya Suma, Yasutaka Anraku, Kotaro Hayashi, Mitsuru Naito, Hyun Jin Kim, Ick Chan Kwon, Kanjiro Miyata, Akihiro Kishimura, Kazunori Kataoka

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Vesicular polyion complexes (PICs) were fabricated through self-assembly of rigid cylindrical molecules, small interfering RNAs (siRNAs), with flexible block catiomers of poly(ethylene glycol) (2 kDa) and cationic polyaspartamide derivative (70 units) bearing a 5-aminopentyl side chain. 100 nm-sized siRNA-assembled vesicular PICs, termed siRNAsomes, were fabricated in specific mixing ranges between siRNA and block catiomer. The siRNAsome membrane was revealed to consist of PIC units fulfilling a simple molar ratio (1:2 or 2:3) of block catiomer and siRNA. These ratios correspond to the minimal integer molar ratio to maximally compensate the charge imbalance of PIC, because the numbers of charges per block catiomer and siRNA are +70 and -40, respectively. Accordingly, the ζ-potentials of siRNAsomes prepared at 1:2 and 2:3 were negative and positive, respectively. Cross-section transmission electron microscopic observation clarified that the membrane thicknesses of 1:2 and 2:3 siRNAsomes were 11.0 and 17.2 nm, respectively. Considering that a calculated long-axial length of siRNA is 5.9 nm, these thickness values correspond to the membrane models of two (11.8 nm) and three (17.7 nm) tandemly aligned siRNAs associating with one and two block catiomers, respectively. For biological application, siRNAsomes were stabilized through membrane-cross-linking with glutaraldehyde. The positively charged and cross-linked siRNAsome facilitated siRNA internalization into cultured cancer cells, eliciting significant gene silencing with negligible cytotoxicity. The siRNAsome stably encapsulated dextran as a model cargo macromolecule in the cavity by simple vortex mixing. Confocal laser scanning microscopic observation displayed that both of the payloads were internalized together into cultured cells. These results demonstrate the potential of siRNAsomes as a versatile platform for codelivery of siRNA with other cargo macromolecules.

Original languageEnglish
Pages (from-to)3699-3709
Number of pages11
JournalJournal of the American Chemical Society
Volume141
Issue number8
DOIs
Publication statusPublished - 2019 Feb 27
Externally publishedYes

Fingerprint

RNA Interference
Macromolecules
Self assembly
Small Interfering RNA
Polyethylene glycols
Membranes
RNA
Bearings (structural)
Cells
Dextran
Cytotoxicity
Vortex flow
Genes
Cultured Cells
Derivatives
Scanning
Molecules
Electrons
Lasers
Ethylene Glycol

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Self-Assembly of siRNA/PEG- b-Catiomer at Integer Molar Ratio into 100 nm-Sized Vesicular Polyion Complexes (siRNAsomes) for RNAi and Codelivery of Cargo Macromolecules. / Kim, Beob Soo; Chuanoi, Sayan; Suma, Tomoya; Anraku, Yasutaka; Hayashi, Kotaro; Naito, Mitsuru; Kim, Hyun Jin; Kwon, Ick Chan; Miyata, Kanjiro; Kishimura, Akihiro; Kataoka, Kazunori.

In: Journal of the American Chemical Society, Vol. 141, No. 8, 27.02.2019, p. 3699-3709.

Research output: Contribution to journalArticle

Kim, BS, Chuanoi, S, Suma, T, Anraku, Y, Hayashi, K, Naito, M, Kim, HJ, Kwon, IC, Miyata, K, Kishimura, A & Kataoka, K 2019, 'Self-Assembly of siRNA/PEG- b-Catiomer at Integer Molar Ratio into 100 nm-Sized Vesicular Polyion Complexes (siRNAsomes) for RNAi and Codelivery of Cargo Macromolecules', Journal of the American Chemical Society, vol. 141, no. 8, pp. 3699-3709. https://doi.org/10.1021/jacs.8b13641
Kim, Beob Soo ; Chuanoi, Sayan ; Suma, Tomoya ; Anraku, Yasutaka ; Hayashi, Kotaro ; Naito, Mitsuru ; Kim, Hyun Jin ; Kwon, Ick Chan ; Miyata, Kanjiro ; Kishimura, Akihiro ; Kataoka, Kazunori. / Self-Assembly of siRNA/PEG- b-Catiomer at Integer Molar Ratio into 100 nm-Sized Vesicular Polyion Complexes (siRNAsomes) for RNAi and Codelivery of Cargo Macromolecules. In: Journal of the American Chemical Society. 2019 ; Vol. 141, No. 8. pp. 3699-3709.
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abstract = "Vesicular polyion complexes (PICs) were fabricated through self-assembly of rigid cylindrical molecules, small interfering RNAs (siRNAs), with flexible block catiomers of poly(ethylene glycol) (2 kDa) and cationic polyaspartamide derivative (70 units) bearing a 5-aminopentyl side chain. 100 nm-sized siRNA-assembled vesicular PICs, termed siRNAsomes, were fabricated in specific mixing ranges between siRNA and block catiomer. The siRNAsome membrane was revealed to consist of PIC units fulfilling a simple molar ratio (1:2 or 2:3) of block catiomer and siRNA. These ratios correspond to the minimal integer molar ratio to maximally compensate the charge imbalance of PIC, because the numbers of charges per block catiomer and siRNA are +70 and -40, respectively. Accordingly, the ζ-potentials of siRNAsomes prepared at 1:2 and 2:3 were negative and positive, respectively. Cross-section transmission electron microscopic observation clarified that the membrane thicknesses of 1:2 and 2:3 siRNAsomes were 11.0 and 17.2 nm, respectively. Considering that a calculated long-axial length of siRNA is 5.9 nm, these thickness values correspond to the membrane models of two (11.8 nm) and three (17.7 nm) tandemly aligned siRNAs associating with one and two block catiomers, respectively. For biological application, siRNAsomes were stabilized through membrane-cross-linking with glutaraldehyde. The positively charged and cross-linked siRNAsome facilitated siRNA internalization into cultured cancer cells, eliciting significant gene silencing with negligible cytotoxicity. The siRNAsome stably encapsulated dextran as a model cargo macromolecule in the cavity by simple vortex mixing. Confocal laser scanning microscopic observation displayed that both of the payloads were internalized together into cultured cells. These results demonstrate the potential of siRNAsomes as a versatile platform for codelivery of siRNA with other cargo macromolecules.",
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T1 - Self-Assembly of siRNA/PEG- b-Catiomer at Integer Molar Ratio into 100 nm-Sized Vesicular Polyion Complexes (siRNAsomes) for RNAi and Codelivery of Cargo Macromolecules

AU - Kim, Beob Soo

AU - Chuanoi, Sayan

AU - Suma, Tomoya

AU - Anraku, Yasutaka

AU - Hayashi, Kotaro

AU - Naito, Mitsuru

AU - Kim, Hyun Jin

AU - Kwon, Ick Chan

AU - Miyata, Kanjiro

AU - Kishimura, Akihiro

AU - Kataoka, Kazunori

PY - 2019/2/27

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