US EPA

4435678 

Journal Article 

Cytoplasm-responsive delivery systems for siRNA using cell-penetrating peptide nanomicelles 

Okada, H; Ogawa, T; Tanaka, K; Kanazawa, T; Takashima, Y 

2014 

Yes 

Journal of Drug Delivery Science and Technology
ISSN: 1773-2247 

24 

1 

3-11 

WOS:000339928700001 

Arginine-rich cell-penetrating peptides (CPPs) involved in the uptake of large molecules such as proteins. nucleotides and even nanoparticles are non-viral carriers for nucleotides. The core-shell-type polyion complexes with a disulfide cross-linked siRNA to poly(L-lysine) or poly(aspartic acid) respond to a reducing environment and achieve higher siRNA transfection efficiency. We synthesized a stable analog of transactivator of transcription (Tat) and a cytoplasm-responsive CPP, CH2R4H2C (C. cysteine [Cys]; H. histamine [His]; R. arginine [Arg]). having 2 Cys residues (for physically trapping in micelles by disulfide linkage): we conjugated the CPP with stearic acid for topical administration or with methoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone) for sustained systemic circulation. Nucleotides were rigidly shielded in the surface of nanomicelles, protected against nucleases in the blood, and persistently released into the reductive environment of the cytoplasm (glutathione, 0.5-10 mM). In this review, we describe DNA vaccination and delivery of siRNA into the cytoplasm using these functional CPP-conjugated nanomicelles. 

DNA vaccine; siRNA therapy; Local and systemic delivery; Polymer micelles; Functional cell-penetrating peptide; Cytoplasm-responsive nanocarriers