Polyrotaxane-based multi-step transformable materials for the delivery of Cas9 ribonucleoprotein

Taharabaru, Toru; Kihara, Takeshi; Onodera, Risako; Kogo, Tetsuya; Higashi, Kenjirou; Moribe, Kunikazu; Nakamura, Teruya; Motoyama, Keiichi; Higashi, Taishi

doi:10.1016/j.apmt.2022.101488

Cited by 8 publications

(17 citation statements)

References 34 publications

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“…11 Nevertheless, the delivery of the RNP also faces many difficulties: RNP is easily denatured and has negligible intracellular delivery activity due to the high molecular weight of Cas9 (160 kDa) and sgRNA (∼31 kDa, ∼130 bases). [12][13][14] Thus, there is an urgent need to develop nanovectors to simultaneously protect RNP from undesired degradation and enhance the efficiency of its intracellular delivery.…”

Section: Introductionmentioning

confidence: 99%

A quaternary ammonium-based nanosystem enables delivery of CRISPR/Cas9 for cancer therapy

Zhang,

Sun,

Liang

et al. 2024

Biomater. Sci.

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Section: Introductionmentioning

confidence: 99%

A quaternary ammonium-based nanosystem enables delivery of CRISPR/Cas9 for cancer therapy

Zhang,

Sun,

Liang

et al. 2024

Biomater. Sci.

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“…[31] Simple multitopic guest-based pseudorotaxanes typically comprise non-specific binding motifs. [32][33][34][35] While these structures are of particular interest in material sciences due to their polymeric nature, [36][37][38] recent advancements have introduced guest molecules featuring multiple specific binding motifs with varying selectivity towards macrocyclic compounds. This innovation enables the construction of functionalised supramolecular structures such as molecular machines, [39] room-temperature phosphorescence switches, [40,41] probes [42] and rotaxane catalysts.…”

Section: Introductionmentioning

confidence: 99%

para–Phenylenediamine Dimer as a Redox–Active Guest for Supramolecular Systems

Janovský,

Springer,

Filip

et al. 2024

Chemistry A European J

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Redox‐active components are highly valuable in the construction of molecular devices. We combined two p‐phenylenediamines (p‐PDA) with a biphenyl (BiPhe) unit to prepare a supramolecular guest 4 consisting of three binding sites for cucurbit[7/8]uril (CBn) and/or cyclodextrins (CD). Supramolecular properties of 4 were investigated using NMR, UV‐vis, mass spectrometry and isothermal titration calorimetry. Our analysis revealed that 4 forms higher‐order host–guest complexes, wherein a CD unit occupies the central BiPhe site, secured by two CBn units at the terminal p‐PDA sites. Additionally, 1:1 complexes with α‐CD and β‐CD, a 1:2 complex with γ‐CD and 2:1 complexes with CB7 and CB8 were identified. Through UV‐vis and cyclic voltammetry, redox processes leading to the formation of a stable, deep blue dication diradical of 4 are elucidated. Furthermore, it is demonstrated that CB7 selectively protects oxidised 4 from reduction in the presence of a reducing agent. The supramolecular and redox properties of the structural motif represented by 4 render it an interesting candidate for the construction of supramolecular devices.

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“…To exhibit RNAi effects and subsequent cytotoxic activity, siPLK-1 should be released from the polyplex. Here, Fol-PRXs include carbamate in the axile molecules, and it can be degraded by carboxylesterase . This leads to the degradation of Fol-PRXs and probably results in the release of siPLK-1.…”

mentioning

confidence: 99%

“…First, to prepare axile molecules of Fol-PRXs, terminals of PEGs were aminated with ethylenediamine through carbamate because it shows long-term biodegradability by carboxylesterase. 12 In addition, relatively high-molecular-weight PEGs (10, 20, or 35 kDa) were selected because they allow low-density CD coverage that is advantageous for moving the CD molecule in PRX. 13 Then, PRXs were prepared by threading α-CD and a subsequent end-cap reaction with Ad.…”

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confidence: 99%

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Stabilization and Movable Ligand-Modification by Folate-Appended Polyrotaxanes for Systemic Delivery of siRNA Polyplex

et al. 2022

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To achieve a systemic targeted delivery of siRNA using polymeric carriers, there is a dilemma between ligand modification and stabilization of the polyplex. Namely, ligand modification often leads to destabilization of the polyplex in the blood circulation. In fact, we previously developed cyclodextrin (CD)/polyamidoamine dendrimer conjugates (CDE) as siRNA carriers, and the interaction of CDE/siRNA was decreased by the conjugation with folate-polyethylene glycol, leading to the destabilization. To overcome this dilemma, in this study, folateappended polyrotaxanes (Fol-PRX) were developed. Fol-PRX stabilized CDE/siRNA polyplex by intermolecularly connecting CDE molecules through a host−guest interaction between adamantane at the terminals of Fol-PRX and β-CD in the polyplex. Moreover, the intermolecular connection of the polyplex with Fol-PRX provided movable folate moieties on the surface. As a result, Fol-PRXs enhanced the in vivo antitumor activity of the polyplex after intravenous administration, suggesting their utility as the dualfunctional materials for systemic delivery of siRNA polyplexes.

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Polyrotaxane-based multi-step transformable materials for the delivery of Cas9 ribonucleoprotein

Cited by 8 publications

References 34 publications

A quaternary ammonium-based nanosystem enables delivery of CRISPR/Cas9 for cancer therapy

A quaternary ammonium-based nanosystem enables delivery of CRISPR/Cas9 for cancer therapy

para–Phenylenediamine Dimer as a Redox–Active Guest for Supramolecular Systems

Stabilization and Movable Ligand-Modification by Folate-Appended Polyrotaxanes for Systemic Delivery of siRNA Polyplex

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