title: Synthetic low-density lipoprotein (sLDL) selectively delivers paclitaxel to tumor with low systemic toxicity.
abstract: Low density lipoprotein (LDL), which is a principal carrier for the delivery of cholesterol, has been used as a great candidate for the delivery of drugs to tumor based on the great requirements for cholesterol of many cancer cells. Mimicking the structure and composition of LDL, we designed a synthetic low-density lipoprotein (sLDL) to encapsulate paclitaxel-alpha linolenic acid (PALA) for tumor therapy. The PALA loaded sLDL (PALA-sLDL) and PALA-loaded microemulsion (PALA-ME, without the binding domain for LDLR) displayed uniform sizes with high drug loading efficiency (> 90%). In vitro studies demonstrated PALA-sLDL exhibited enhanced cellular uptake capacity and better cytotoxicity to LDLR over-expressed U87 MG cells as compared to PALA-ME. The uptake mechanisms of PALA-sLDL were involved in a receptor mediated endocytosis and macropinocytosis. Furthermore, the in vivo biodistribution and tumor growth inhibition studies of PALA-sLDL were investigated in xenograft U87 MG tumor-bearing mice. The results showed that PALA-sLDL exhibited higher tumor accumulation than PALA-ME and superior tumor inhibition efficiency (72.1%) compared to Taxol® (51.2%) and PALA-ME (58.8%) but with lower toxicity. These studies suggested that sLDL is potential to be used as a valuable carrier for the selective delivery of anticancer drugs to tumor with low systemic toxicity.
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Su
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
authors.forename: De-Sheng
authors.initials: DS
authors.lastname: Liang
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.|State Key Laboratory of Natural and Biomimetic Drugs, Beijing, 100191, PR China.
authors.forename: Xian-Rong
authors.initials: XR
authors.lastname: Qi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000009:adverse effects / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000009:adverse effects; D056945:Hep G2 Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects*; D010316:Particle Size; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008077:Lipoproteins, LDL; D008823:Micelles; D017239:Paclitaxel
keywords: PTX-alpha linolenic acid (PALA); anti-tumor efficacy; biomimetic; low systemic toxicity; synthetic low-density lipoprotein (sLDL)