Carrier-free nanodrug targeting glucose metabolism for enhanced rheumatoid arthritis treatment

Abstract

Dramatically increased glycolysis has been found in inflamed joints in rheumatoid arthritis (RA) due to the increased demand for energy and biosynthetic precursors to support the expansion of inflammation. Therefore, regulating the elevated glycolysis level in RA progress might hold potential to achieve inflammation remission. 2-deoxy-D-glucose (2-DG) is a well-characterized glycolysis inhibitor. However, the rapid clearance and indiscriminate distribution of 2-DG have hampered its application. Although nanocarriers can facilitate targeted delivery to improve drug bioavailability, they often suffer from undesirable drug loading and potential toxicity caused by carrier materials. Thus, carrier-free nanodrugs formed by pure therapeutic drugs with satisfying biological activity might possess promising potential for RA therapy. Herein, we reported the carrier-free nanodrug self-assembled from 2-DG and Curcumin (Cur) without any other ingredient. Cur is a natural anti-inflammatory agent and has been widely investigated for inflammatory diseases therapy. The self-assembly of 2-DG/Cur nanodrug (2-DCNP) does not require any additional material. Therefore, the application of 2-DCNP can avoid the potential side effects caused by carrier materials. Inflammatory cells usually exhibited high expression of glucose transporter protein 1 (GLUT1) to facilitate glucose utilization. Thus, 2-DCNP with 2-DG on the surface might promote selective drug delivery to inflamed joints due to the high affinity between 2-DG and GLUT1. Our results indicated that 2-DCNP treatment could effectively inhibit glycolysis level to finally achieve desirable therapeutic efficacy in arthritic rats. This carrier-free nanodrug aiming at regulating glucose metabolism in inflamed joints might provide new insight for RA therapy.

Keywords: 2-Deoxy-D-glucose; Carrier-free nanodrug; Drug delivery; Glycolysis; Rheumatoid arthritis.