Protein-nanoparticle conjugates as potential therapeutic agents for the treatment of hyperlipidemia.
Hyperlipidemia, a condition associated with atherosclerosis, can develop because of the lack of low density lipoprotein (LDL) receptors in hepatocytes. Since injected polymeric nanoparticles are quickly taken up by the liver Kupffer cells, we hypothesize that it is possible to enhance LDL delivery to the liver through the use of LDL-absorbing nanoparticles. Here, we demonstrate the feasibility of the proposed approach in vitro. We used biodegradable and biocompatible polylactide nanoparticles (approximately 100 nm in diameter) with covalently attached apolipoprotein B100 antibody to adsorb LDLs at physiologically relevant concentrations. We showed that up to sixfold decreases of LDL levels can be achieved in vitro upon treatment of LDL suspensions (500 mg dl( - 1)) with anti-apoB100-nanoparticle conjugates. The study of the uptake of the antibody-nanoparticle-LDL complexes by cells was performed using a mouse macrophage cell line (RAW 264.7) as a model for liver Kupffer cells. We found that macrophages can quickly take up antibody-nanoparticle-LDL complexes and digest them within 24 h. No evidence of cytotoxicity was observed for the experimental conditions used in this study.
Department of Bioengineering, Clemson University, Clemson, SC 29631, USA.
V D
VD
Maximov
V V
VV
Reukov
J N
JN
Barry
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C
Cochrane
A A
AA
Vertegel
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D053299:Apolipoprotein B-100 / Q000276:immunology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D006949:Hyperlipidemias / Q000628:therapy*; D008027:Light; D008077:Lipoproteins, LDL / Q000627:therapeutic use*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000627:therapeutic use* / Q000648:ultrastructure; D010316:Particle Size; D011091:Polyesters / Q000494:pharmacology; D012542:Scattering, Radiation; D013997:Time Factors; D017186:Titrimetry
D000906:Antibodies; D053299:Apolipoprotein B-100; D008077:Lipoproteins, LDL; D011091:Polyesters; C033616:poly(lactide)