title: Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ɛ-caprolactone) nanoparticles.
abstract: Nanoscale drug carriers have been extensively developed to improve drug therapeutic efficiency. However, delivery of chemotherapeutic agents to tumor tissues and cells has not been favorably managed. In this study, we developed a novel "intelligent" nanoparticle, consisting of a gelatinase-cleavage peptide with poly(ethylene glycol) (PEG) and poly(ɛ-caprolactone) (PCL)-based structure for tumor-targeted docetaxel delivery (DOC-TNPs). The docetaxel-loaded PEG-PCL nanoparticles (DOC-NPs) that did not display gelatinase-stimuli behaviors were used as a control. We found clear evidence that the DOC-TNPs were transformed by gelatinases, allowing drug release and enhancing the cellular uptake of DOC (P < 0.01). In vivo biodistribution study demonstrated that targeted DOC-TNPs could accumulate and remain in the tumor regions, whereas non-targeted DOC-NPs rapidly eliminated from the tumor tissues. DOC-TNPs exhibited higher tumor growth suppression than commercialized Taxotere(®) (docetaxel; Jiangsu Hengrui Medicine Company, Jiangsu, China) and DOC-NPs on hepatic H22 tumor model via intravenous administration (P < 0.01). Both in vitro and in vivo experiments suggest that the gelatinase-mediated nanoscale delivery system is promising for improvement of antitumor efficacy in various overexpressed gelatinase cancers.
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Ru-Tian
authors.initials: RT
authors.lastname: Li
authors.forename: Han-Qing
authors.initials: HQ
authors.lastname: Qian
authors.forename: Mi
authors.initials: M
authors.lastname: Yang
authors.forename: Zhen-Shu
authors.initials: ZS
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Qian
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Yu
authors.forename: Xi-Qun
authors.initials: XQ
authors.lastname: Jiang
authors.forename: Bao-Rui
authors.initials: BR
authors.lastname: Liu
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001672:Biocompatible Materials; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D018093:Gelatinases / Q000737:chemistry*; D006801:Humans; D007275:Injections, Intravenous; D008114:Liver Neoplasms, Experimental / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D064847:Multimodal Imaging; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D049268:Positron-Emission Tomography; D011897:Random Allocation; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D043823:Taxoids; D000077143:Docetaxel; D018093:Gelatinases