Drug Carrier

According to Experiment 4 - in vitro, the structure of nanoparticles can be easily endocytosed by macrophages and thus achieve the targeting goal, while not penetrating other cells.

We then came up with an idea that maybe we can utilize the central hydrophobic part in JS-1, with the protection of a hydrophilic PEG, to carry hydrophobic small molecular drugs into macrophages.

To further examine our hypothesis, we used “Imperatorin” in the following experiments [1]. It’s a hydrophobic small molecule immune suppressor that can block the expression of iNOS and COX2 protein and inhibit the production of NO.

We induced acute hepatitis in mice by LPS/D-Gal, and took the macrophages of mice as a model. The six groups we designed were as follows: control group (Non-LPS-induced), control group (LPS-induced), Imperatorin only, JS-1 only, Imperatorin-encapsulated JS-1, and JS-1-Imperatorin copolymers. We then measured their NO concentration (Figure. I-1, by Griess assay), and iNOS and COX2 protein expressions (Figure. I-2, by Western blot).

Figure. I-1. Griess assay: only JS-1, Imperatorin-encapsulated JS-1, and JS-1-Imperatorin copolymer groups are significant, decreasing obviously. Moreover, the NO production concentration decreased the most in the Imperatorin-encapsulated JS-1 group.

Figure. I-2. Western Blot (compared with β-actin): The iNOS and COX2 protein expression decreased the most in Imperatorin-encapsulated JS-1 group.

Based on the results, the “Imperatorin-encapsulated JS-1” group exhibits best suppression effect. We can tell from the result that JS-1 acts well as a drug carrier. It carries a hydrophobic small molecular drug into the cell while both of their structure still remain intact, therefore achieving better drug efficacy.

We believe that this design could be applied to enhance drug efficacy and control HuR and other pathogenicity genes or proteins at the same time.

Reference:

  1. Huang GJ, Deng JS, Liao JC, Hou WC, Wang SY, Sung PJ, Kuo YH., Inducible nitric oxide synthase and cyclooxygenase-2 participate in anti-inflammatory activity of imperatorin from Glehnia littoralis., J Agric Food Chem. 2012 Feb 22;60(7):1673-81. doi: 10.1021/jf204297e. Epub 2012 Feb 8.