title: A biodistribution study of solid lipid-polyethyleneimine hybrid nanocarrier for cancer RNAi therapy.
abstract: Solid lipid-polymer hybrid nanocarrier (LPN) was previously reported to achieve high siRNA transfection efficiency and induce sustained RNAi-based chemosensitizing effect at cellular level. In this study, our objectives were to evaluate the in vivo biodistribution of LPNs in a prostate cancer model and determine the factors that potentially affect tumor penetration by LPNs. The LPN formulation with the highest transfection efficiency (64%) and stability was selected for the study. Mice bearing tumors of PC-3Mcells were treated with LPNs labeled with IR780 or AF647-siRNA. Near infrared imaging showed that LPNs achieved favorable in vivo biodistribution with high tumor/low organ ratios. LPN accumulation was also observed in liver metastatic tissue. Result of extravasation study confirmed that encapsulated siRNA molecules were able to escape into the tumor tissue at the extravascular area. When LPN levels in large (volume>750mm3) and small (<500mm3) tumors were compared, no significant difference was observed. However, both docetaxel pretreatment (72hbefore LPN) and concurrent docetaxel treatment significantly enhanced the tumor LPN levels by 3.9- and 3.1-fold, respectively (both p<0.01). In conclusion, LPN is a promising carrier system to deliver RNAi therapy to solid malignancies that also receive chemotherapy.
authors: School of Pharmacy, Temple University, 3307 North Broad Street, Philadelphia, PA 19140, United States.
authors: Hui Yi
authors: HY
authors: Xue
authors: School of Pharmacy, Temple University, 3307 North Broad Street, Philadelphia, PA 19140, United States.
authors: Ngoc
authors: N
authors: Tran
authors: School of Pharmacy, Temple University, 3307 North Broad Street, Philadelphia, PA 19140, United States. Electronic address: holunwong2011@yahoo.com.
authors: Ho Lun
authors: HL
authors: Wong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004815:Epidermal Growth Factor / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D051379:Mice; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011094:Polyethyleneimine / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011897:Random Allocation; D043823:Taxoids / Q000008:administration & dosage; D014162:Transfection
chemical_list: D008055:Lipids; D034741:RNA, Small Interfering; D043823:Taxoids; D000077143:Docetaxel; D004815:Epidermal Growth Factor; D011094:Polyethyleneimine
keywords: Biodistribution; Cancer therapy; Chemotherapy; Drug delivery; Hybrid nanocarrier; Lipid nanoparticles; Solid tumor; Tumor priming; siRNA