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Artif Cells Nanomed Biotechnol. 2018 Dec;46(8):1605-1616. doi: 10.1080/21691401.2017.1384385. Epub 2017 Oct 3.

L-Carnitine-conjugated nanoparticles to promote permeation across blood-brain barrier and to target glioma cells for drug delivery via the novel organic cation/carnitine transporter OCTN2.

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a Municipal Key Laboratory of Biopharmaceutics, Wuya College of Innovation , Shenyang Pharmaceutical University , Shenyang , China.
b Department of Cell Biology and Biochemistry , Texas Tech University Health Sciences Center , Lubbock , TX , USA.
c Department of Pharmaceutics, Wuya College of Innovation , Shenyang Pharmaceutical University , Shenyang , China.


Overcoming blood-brain barrier (BBB) and targeting tumor cells are two key steps for glioma chemotherapy. By taking advantage of the specific expression of Na+-coupled carnitine transporter 2 (OCTN2) on both brain capillary endothelial cells and glioma cells, l-carnitine conjugated poly(lactic-co-glycolic acid) nanoparticles (LC-PLGA NPs) were prepared to enable enhanced BBB permeation and glioma-cell targeting. Conjugation of l-carnitine significantly enhanced the uptake of PLGA nanoparticles in the BBB endothelial cell line hCMEC/D3 and the glioma cell line T98G. The uptake was dependent on Na+ and inhibited by the excessive free l-carnitine, suggesting involvement of OCTN2 in the process. In vivo mouse studies showed that LC-PLGA NPs resulted in high accumulation in the brain as indicated by the biodistribution and imaging assays. Furthermore, compared to Taxol and paclitaxel-loaded unmodified PLGA NPs, the drug-loaded LC-PLGA NPs showed improved anti-glioma efficacy in both 2D-cell and 3D-spheroid models. The PEG spacer length of the ligand attached to the nanoparticles was optimized, and the formulation with PEG1000 (LC-1000-PLGA NPs) showed the maximum targeting efficiency. We conclude that l-carnitine-mediated cellular recognition and internalization via OCTN2 significantly facilitate the transcytosis of nanoparticles across BBB and the uptake of nanoparticles in glioma cells, resulting in improved anti-glioma efficacy.


OCTN2; blood-brain barrier; glioma cells; l-Carnitine; nanoparticles; transporter-mediated endocytosis

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