title: Targeted intracellular delivery of resveratrol to glioblastoma cells using apolipoprotein E-containing reconstituted HDL as a nanovehicle.
abstract: The objective of this study is to transport and deliver resveratrol to intracellular sites using apolipoprotein E3 (apoE3). Reconstituted high-density lipoprotein (rHDL) bearing resveratrol (rHDL/res) was prepared using phospholipids and the low-density lipoprotein receptor (LDLr)-binding domain of apoE3. Biophysical characterization revealed that resveratrol was partitioned into the phospholipid bilayer of discoidal rHDL/res particles (~19 nm diameter). Co-immunoprecipitation studies indicated that the LDLr-binding ability of apoE3 was retained. Cellular uptake of resveratrol to intracellular sites was evaluated in glioblastoma A-172 cells by direct fluorescence using chemically synthesized NBD-labeled resveratrol (res/NBD) embedded in rHDL/res. Competition and inhibition studies indicate that the uptake is by receptor mediated endocytosis via the LDLr, with co-localization of apoE3 and res/NBD in late endosomes/lysosomes. We propose that rHDL provides an ideal hydrophobic milieu to sequester resveratrol and that rHDL containing apoE3 serves as an effective "nanovehicle" to transport and deliver resveratrol to targeted intracellular sites.
authors.affiliation: Department of Chemistry and Biochemistry, California State University Long Beach, Long Beach, California, United States of America.
authors.forename: Sea H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Biochemistry, California State University Long Beach, Long Beach, California, United States of America.
authors.forename: Birendra Babu
authors.initials: BB
authors.lastname: Adhikari
authors.affiliation: Department of Chemistry and Biochemistry, California State University Long Beach, Long Beach, California, United States of America.
authors.forename: Siobanth
authors.initials: S
authors.lastname: Cruz
authors.affiliation: Department of Chemistry and Biochemistry, California State University Long Beach, Long Beach, California, United States of America.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schramm
authors.affiliation: Chemistry Department, Loyola Science Center, University of Scranton, Scranton, Pennsylvania, United States of America.
authors.forename: Joe A
authors.initials: JA
authors.lastname: Vinson
authors.affiliation: Department of Chemistry and Biochemistry, California State University Long Beach, Long Beach, California, United States of America.
authors.forename: Vasanthy
authors.initials: V
authors.lastname: Narayanaswami
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000494:pharmacology*; D053318:Apolipoprotein E3 / Q000737:chemistry / Q000378:metabolism*; D001393:Azoles; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D005456:Fluorescent Dyes; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009578:Nitrobenzenes; D010316:Particle Size; D017434:Protein Structure, Tertiary; D011973:Receptors, LDL / Q000737:chemistry / Q000378:metabolism; D000077185:Resveratrol; D013194:Staining and Labeling / Q000379:methods; D013267:Stilbenes / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C510797:7-nitrobenz-2-oxa-1,3-diazol-4-yl; D000972:Antineoplastic Agents, Phytogenic; D053318:Apolipoprotein E3; D001393:Azoles; D005456:Fluorescent Dyes; D008075:Lipoproteins, HDL; D009578:Nitrobenzenes; D011973:Receptors, LDL; D013267:Stilbenes; D000077185:Resveratrol