title: Tumor-targeted delivery of paclitaxel using low density lipoprotein-mimetic solid lipid nanoparticles.
abstract: Water-insoluble anticancer drugs, including paclitaxel, present severe clinical side effects when administered to patients, primarily associated with the toxicity of reagents used to solubilize the drugs. In efforts to develop alternative formulations of water-insoluble anticancer drugs suitable for intravenous administration, we developed biocompatible anticancer therapeutic solid lipid nanoparticles (SLNs), mimicking the structure and composition of natural particles, low-density lipoproteins (LDLs), for tumor-targeted delivery of paclitaxel. These therapeutic nanoparticles contained water-insoluble paclitaxel in the core with tumor-targeting ligand covalently conjugated on the polyethylene glycol (PEG)-modified surface (targeted PtSLNs). In preclinical human cancer xenograft mouse model studies, the paclitaxel-containing tumor-targeting SLNs exhibited pronounced in vivo stability and enhanced biocompatibility. Furthermore, these SLNs had superior antitumor activity to in-class nanoparticular therapeutics in clinical use (Taxol and Genexol-PM) and yielded long-term complete responses. The in vivo targeted antitumor activities of the SLN formulations in a mouse tumor model suggest that LDL-mimetic SLN formulations can be utilized as a biocompatible, tumor-targeting platform for the delivery of various anticancer therapeutics.
authors: †Medical Nanoelement Development Center, Samsung Biomedical Research Institute, Seoul 135-710, Republic of Korea.|‡Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, Republic of Korea.
authors: Jin-Ho
authors: JH
authors: Kim
authors: †Medical Nanoelement Development Center, Samsung Biomedical Research Institute, Seoul 135-710, Republic of Korea.
authors: Youngwook
authors: Y
authors: Kim
authors: §Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
authors: Ki Hyun
authors: KH
authors: Bae
authors: §Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
authors: Tae Gwan
authors: TG
authors: Park
authors: ‡Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, Republic of Korea.|∥Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors: Jung Hee
authors: JH
authors: Lee
authors: †Medical Nanoelement Development Center, Samsung Biomedical Research Institute, Seoul 135-710, Republic of Korea.|⊥Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors: Keunchil
authors: K
authors: Park
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis; D001672:Biocompatible Materials / Q000737:chemistry; D032701:Biomimetics; D045744:Cell Line, Tumor; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D008055:Lipids; D008077:Lipoproteins, LDL; D014867:Water; D011092:Polyethylene Glycols; D017239:Paclitaxel
keywords: cancer therapy; paclitaxel; solid lipid nanoparticles; targeted drug delivery system; tumor targeting