Synthetic nano-LDL with paclitaxel oleate as a targeted drug delivery vehicle for glioblastoma multiforme.
The low density lipoprotein (LDL) receptor has been shown to be upregulated in GBM tumor cells in vitro and is therefore a potential molecular target for the delivery of therapeutic agents. A synthetic nano-LDL (nLDL) particle was developed as a drug delivery vehicle targeted to GBM cells by incorporating a lipophilic prodrug, paclitaxel oleate, into the particle. Nano-LDL containing paclitaxel oleate (nLDL-PO) was constructed by combining a synthetic peptide containing a lipid binding motif and the LDL receptor (LDLR) binding domain of apolipoprotein B-100 with a lipid emulsion consisting of phosphatidyl choline, triolein, and paclitaxel oleate. Paclitaxel oleate incorporated into the core of the lipid particle. nLDL-PO cell survival in GBM cell lines was found to be time, concentration, and cell line dependent. Cell killing was observed with short drug incubations and exhibited saturation at 6 h. nLDL-PO cell survival improved in the presence of the LDL receptor inhibitor, suramin, demonstrating that the drug was delivered via the LDL receptor. Collectively, these data strongly suggest that the synthetic nano-LDLs can incorporate lipophilic drugs and are capable of killing GBM cells. nLDL-PO has the potential to serve as a selective drug delivery vehicle for targeting GBM tumors via the LDL receptor.
Nikanjam
Mina
M
Department of Bioengineering, University of California, Berkeley, California, United States.
Gibbs
Andrew R
AR
Hunt
C Anthony
CA
Budinger
Thomas F
TF
Forte
Trudy M
TM
D000596:Amino Acids; D000970:Antineoplastic Agents / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004655:Emulsions; D005240:Feasibility Studies; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D020128:Inhibitory Concentration 50; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D019301:Oleic Acid / Q000737:chemistry; D017239:Paclitaxel / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D010316:Particle Size; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011973:Receptors, LDL / Q000737:chemistry
D000596:Amino Acids; D000970:Antineoplastic Agents; D004655:Emulsions; D005456:Fluorescent Dyes; D008077:Lipoproteins, LDL; D010455:Peptides; D014677:Pharmaceutical Vehicles; D011973:Receptors, LDL; D019301:Oleic Acid; D016650:Fluorescein-5-isothiocyanate; D017239:Paclitaxel