Kim Jin-Ho, Kim Youngwook, Bae Ki Hyun, Park Tae Gwan, Lee Jung Hee, Park Keunchil
†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.
Mol Pharm. 2015 Apr 6;12(4):1230-41. doi: 10.1021/mp500737y. Epub 2015 Mar 7.
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.
包括紫杉醇在内的水不溶性抗癌药物在给患者使用时会产生严重的临床副作用，主要与用于溶解药物的试剂的毒性有关。为了开发适合静脉给药的水不溶性抗癌药物的替代制剂，我们开发了生物相容性抗癌治疗性固体脂质纳米颗粒（SLN），模仿天然颗粒低密度脂蛋白（LDL）的结构和组成，用于紫杉醇的肿瘤靶向递送。这些治疗性纳米颗粒在核心含有水不溶性紫杉醇，肿瘤靶向配体共价偶联在聚乙二醇（PEG）修饰的表面（靶向PtSLN）。在临床前人类癌症异种移植小鼠模型研究中，含紫杉醇的肿瘤靶向SLN表现出显著的体内稳定性和增强的生物相容性。此外，这些SLN比临床使用的同类纳米颗粒治疗剂（紫杉醇和Genexol-PM）具有更好的抗肿瘤活性，并产生长期的完全缓解。SLN制剂在小鼠肿瘤模型中的体内靶向抗肿瘤活性表明，模仿LDL的SLN制剂可作为一种生物相容性、肿瘤靶向平台，用于递送各种抗癌治疗剂。
