title: Enhanced antitumor efficacy, biodistribution and penetration of docetaxel-loaded biodegradable nanoparticles.
abstract: To investigate the antitumor effect, biodistribution and penetration in tumors of docetaxel (DOC)-loaded polyethylene glycol-poly(caprolactone) (mPEG-PCL) nanoparticles on hepatic cancer model, DOC-loaded nanoparticles (DOC-NPs) were prepared with synthesized mPEG-PCL by nano-precipitated method with satisfactory encapsulation efficiency, loading capacity and size distribution. The fabricated nano-drugs were effectively transported into tumoral cells through endocytosis and localized around the nuclei in the cytoplasm. In vitro cytotoxicity test showed that DOC-NPs inhibited the murine hepatic carcinoma cell line H22 in a dose-dependent manner, which was similar to Taxotere, the commercialized formulation of docetaxel. The in vivo biodistribution performed on tumor-bearing mice by NIRF real-time imaging demonstrated that the nanoparticles achieved higher concentration and longer retention in tumors than in non-targeted organs after intravenous injection. The immunohistochemical analysis demonstrated that the nanoparticles located not only near the tumoral vasculatures, but also inside the tumoral interior. Therefore, DOC-NPs could penetrate into tumor parenchyma, leading to high intratumoral concentration of DOC. More importantly, the in vivo anti-tumor evaluation showed that DOC-NPs significantly inhibited tumor growth by tumor volume measurement and positron emission tomography and computed tomography (PET/CT) imaging observation. Taken together, the reported drug delivery system here could shed light on the future targeted therapy against hepatic carcinoma.
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Rutian
authors.initials: R
authors.lastname: Li
authors.forename: Zhenshu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Qian
authors.forename: Wenxian
authors.initials: W
authors.lastname: Guan
authors.forename: Lixia
authors.initials: L
authors.lastname: Yu
authors.forename: Mi
authors.initials: M
authors.lastname: Yang
authors.forename: Xiqun
authors.initials: X
authors.lastname: Jiang
authors.forename: Baorui
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D000077143:Docetaxel; D004337:Drug Carriers; D004339:Drug Compounding; D004705:Endocytosis; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D064847:Multimodal Imaging; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D049268:Positron-Emission Tomography; D019265:Spectroscopy, Near-Infrared; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D011091:Polyesters; D043823:Taxoids; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D000077143:Docetaxel; D011092:Polyethylene Glycols