Efficient gene delivery by urocanic acid-modified chitosan

Aerosol delivery of urocanic acid–modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice

“…Moreover, it has low transfection efficiency, resulting from inefficient release of chitosan/DNA complex from endocytic vesicles into cytoplasm (14). To take advantage of the benefits chitosan offers while minimizing its negative effects, we previously developed UAC, a modified chitosan, as a novel gene carrier and showed its biocompatibility gene delivery efficiency (15). In this study, we confirmed low cytotoxicity of UAC (Fig.…”

“…Results UAC, with Its Low Toxicity and Good DNA Carrying Capacity, Is a Suitable Carrier for Gene Delivery Nuclear magnetic resonance spectra confirmed successful synthesis of UAC and the substitution degree obtained of urocanic acid coupled with chitosan was f37.4 mole % of amine groups in chitosan, a value similar to that of UAC70, which had the highest transfection efficiency in a previous study (15). The synthesized UAC exhibited a high capacity for condensing DNA as well as protecting DNA from DNase I attack (data not shown).…”

“…Preparation of UAC and UAC/DNA Complexes UAC was prepared as previously described (15). Briefly, chitosan was coupled with urocanic acid (70 mole %) via an active ester intermediate using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (Peptide Institute, Osaka, Japan).…”

“…However, inefficient release of chitosan/DNA complexes from endocytic vesicles into the cytoplasm is one of the primary causes of poor gene delivery (14). To overcome such obstacle, in a previous study, we have designed imidazole ring-containing urocanic acid -modified chitosan (UAC) and proved the efficiency of UAC for gene delivery in vitro by enhancing the release of UAC/DNA complexes into the cytoplasm following the endosomal rupture through proton sponge mechanism (15). In this study, UAC was adopted as a gene carrier for aerosol gene delivery in attempt to develop a safer and more efficient system for in vivo lung cancer therapy.…”

Urocanic acid-modified chitosan-mediated PTEN delivery via aerosol suppressed lung tumorigenesis in K-rasLA1 mice

“…7 In these regards, we have already shown that urocanic acid (UA)-modified chitosan (UAC) is an effective delivery vehicle due to degradability, ability to form a complex with DNA and its physicochemical properties as a gene delivery system with little toxicity and enhanced gene transfection efficiency. 8,9 Approximately 30% of human tumors carry ras gene mutations. Of the three members of ras family-K-ras, N-ras and H-ras-K-ras are found to be the most frequently mutated members in human tumors, including lung adenocarcinomas (25-50%).…”