Fusogenic liposome delivers encapsulated nanoparticles for cytosolic controlled gene release.
Therapeutic agents based on DNA or RNA oligonucleotides (e.g., antisense DNA oligonucleotide, small interfering RNA) require a regulation of their kinetics in cytoplasm to maintain an optimal concentration during the treatment period. In this respect, delivery of functional nanoparticles containing these drugs into cytoplasm has been thought to have a potential for the cytosolic controlled gene release. In this study, we establish a protocol for the encapsulation of nanoparticles into liposome, which is further fused with ultra violet-inactivated Sendai virus to compose fusogenic liposomes. When nanoparticles were encapsulated in conventional liposomes, endocytosis-mediated uptake of nanoparticles was observed. In contrast, numerous amounts of nanoparticles were delivered into the cytoplasm without any cytotoxicity when the particles were encapsulated in fusogenic liposomes. Additionally, fusogenic liposome showed a high ability to deliver nanoparticles containing DNA oligonucleotides into cytoplasm. These results indicate that this combinatorial nanotechnology using fusogenic liposome and nanoparticle is a valuable system for regulating the intracellular pharmacokinetics of gene-based drugs.
Kunisawa
Jun
J
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Masuda
Takashi
T
Katayama
Kazufumi
K
Yoshikawa
Tomoaki
T
Tsutsumi
Yasuo
Y
Akashi
Mitsuru
M
Mayumi
Tadanori
T
Nakagawa
Shinsaku
S
D000818:Animals; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism*; D004337:Drug Carriers; D004339:Drug Compounding; D005079:Excipients; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D018374:LLC-PK1 Cells; D008081:Liposomes; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009841:Oligonucleotides / Q000008:administration & dosage / Q000493:pharmacokinetics; D011143:Polyvinyl Chloride; D029082:Sendai virus / Q000235:genetics; D013552:Swine
D004337:Drug Carriers; D005079:Excipients; D008081:Liposomes; D009841:Oligonucleotides; D011143:Polyvinyl Chloride