title: The spacer arm length in cell-penetrating peptides influences chitosan/siRNA nanoparticle delivery for pulmonary inflammation treatment.
abstract: Although chitosan and its derivatives have been frequently utilized as delivery vehicles for small interfering RNA (siRNA), it is challenging to improve the gene silencing efficiency of chitosan-based nanoparticles. In this study, we hypothesized that controlling the spacer arm length between a cell-penetrating peptide (CPP) and a nanoparticle could be critical to enhancing the cellular uptake as well as the gene silencing efficiency of conventional chitosan/siRNA nanoparticles. A peptide consisting of nine arginine units (R9) was used as a CPP, and the spacer arm length was controlled by varying the number of glycine units between the peptide (R9Gn) and the nanoparticle (n = 0, 4, and 10). Various physicochemical characteristics of R9Gn-chitosan/siRNA nanoparticles were investigated in vitro. Increasing the spacing arm length did not significantly affect the complex formation between R9Gn-chitosan and siRNA. However, R9G10-chitosan was much more effective in delivering genes both in vitro and in vivo compared with non-modified chitosan (without the peptide) and R9-chitosan (without the spacer arm). Chitosan derivatives modified with oligoarginine containing a spacer arm can be considered as potential delivery vehicles for various genes.
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea. leeky@hanyang.ac.kr rhim@hanyang.ac.kr.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Jeong
authors.forename: Moonhwan
authors.initials: M
authors.lastname: Choi
authors.forename: Jangwook
authors.initials: J
authors.lastname: Lee
authors.forename: Taiyoun
authors.initials: T
authors.lastname: Rhim
authors.forename: Kuen Yong
authors.initials: KY
authors.lastname: Lee
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems; D005109:Extracellular Matrix / Q000378:metabolism; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D005998:Glycine / Q000737:chemistry; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011014:Pneumonia / Q000628:therapy*; D034741:RNA, Small Interfering / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D057846:Cell-Penetrating Peptides; D034741:RNA, Small Interfering; D048271:Chitosan; D001120:Arginine; D005998:Glycine