title: Collagenase-1 injection improved tumor distribution and gene expression of cationic lipoplex.
abstract: Elevated interstitial fluid pressure (IFP) in a tumor is a barrier to tumor accumulation of systemic delivery of nanocarriers. In this study, we investigated whether intravenous injection of type I collagenase (collagenase-1) reduced IFP in tumors and increased the accumulation and gene expression of cationic liposome/plasmid DNA complex (lipoplex) in tumors after intravenous injection into mice bearing mouse lung carcinoma LLC tumors. Collagenase-1 reduced the amount of type I collagen in the tumor, and significantly decreased IFP by 65% at 1h after injection. Therefore, collagenase-1 induced 1.5-fold higher accumulation and 2-fold higher gene expression of lipoplex in tumors after intravenous injection. These findings indicated that intravenous injection of collagenase-1 improved the accumulation of lipoplex by decreasing IFP in tumors. These results support the potential use of collagen digestion as a strategy to improve systemic gene delivery into tumors.
authors.affiliation: Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Mako
authors.initials: M
authors.lastname: Kato
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Manami
authors.initials: M
authors.lastname: Kubo
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D045744:Cell Line, Tumor; D047009:Hathewaya histolytica / Q000201:enzymology*; D024042:Collagen Type I / Q000378:metabolism*; D017364:Collagenases / Q000008:administration & dosage* / Q000302:isolation & purification; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D015316:Genetic Therapy; D007275:Injections, Intravenous; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D003012:Microbial Collagenase / Q000008:administration & dosage* / Q000302:isolation & purification; D011312:Pressure; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection / Q000379:methods*
chemical_list: D024042:Collagen Type I; D004247:DNA; D049409:Luciferases, Firefly; D017364:Collagenases; C417249:collagenase 1; D003012:Microbial Collagenase