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 2024-01-19T21:00:37Z 2024-01-19T21:00:37Z 2022-01-25 2019-02 0002-7863 https://pubs.kist.re.kr/handle/201004/120386 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 zeta-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. English AMER CHEMICAL SOC 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 Article 10.1021/jacs.8b13641 1 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.141, no.8, pp.3699 - 3709 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 141 8 3699 3709 N scie scopus 000460200100049 2-s2.0-85061905468 Chemistry, Multidisciplinary Chemistry Article DELIVERY VEHICLES BLOCK-COPOLYMERS VESICLES INTERFERENCE PAIR THERAPEUTICS POLYMERSOMES ORGANELLE PICSOMES PROGRESS