Hyaluronic acid/polyethyleneimine nanoparticles loaded with copper ion and disulfiram for esophageal cancer

Abstract

In the clinical treatment of cancer, improving the effectiveness and targeting of drugs has always been a bottleneck problem that needs to be solved. In this contribution, inspired by the targeted inhibition on cancer from combination application of disulfiram and divalent copper ion (Cu²⁺), we optimized the concentration of disulfiram and Cu²⁺ ion for inhibiting esophageal cancer cells, and loaded them in hyaluronic acid (HA)/polyethyleneimine (PEI) nanoparticles with specific scales, in order to improve the effectiveness and targeting of drugs. The in vitro cell experiments demonstrated that more drug loaded HA/PEI nanoparticles accumulated to the esophageal squamous cell carcinoma (Eca109) and promoted higher apoptosis ratio of Eca109. Both in vitro and in vivo biological assessment verified that the disulfiram/Cu²⁺ loaded HA/PEI nanoparticles promoted the apoptosis of cancer cells and inhibited the tumor proliferation, but had no toxicity on other normal organs.

Keywords: Disulfiram/Cu(2+); Drug loaded nanoparticles; Effectiveness and targeting; Esophageal cancer; Hyaluronic acid.