Synergistic antitumor efficacy of doxorubicin and gambogic acid-encapsulated albumin nanocomposites

Colloids Surf B Biointerfaces. 2020 Dec:196:111286. doi: 10.1016/j.colsurfb.2020.111286. Epub 2020 Jul 30.

Abstract

Despite the success, the applicability of traditional chemotherapy still faces several challenges in treating cancer-related ailments, such as enormous toxicity and adverse effects. Combinatorial chemotherapy at reduced doses can offer augmented therapeutic efficiency through multiple mechanisms and even substantially circumvents the issues of toxicity and adverse effects. To demonstrate these facts, herein, two kinds of antitumor drugs, doxorubicin (DOX) and gambogic acid (GA), are encapsulated in bovine serum albumin (BSA) nanoparticles distinctly, resulting in DNP and GNP, respectively. These drug-loaded albumin nanocomposites, DNPs, and GNPs, showed a synergistic effect in ablating HepG2 tumor cells at a combination index (CI) of 0.38. Further, the ex vivo fluorescence imaging investigation confirmed the enriched drug internalization in the tumor precisely, which could be due to the enhanced permeation and retention (EPR) effect, resulting in the augmented therapeutic efficiency of designed nanoformulation. Notably, the synergistic tumor inhibition efficacy is more significantly attained at a 3-fold lesser dose of combined treatment than that of single full dose treatment in vivo. As anticipated, these conditions resulted in reduced organ toxicity. Together, this combinatorial strategy using BSA-based composites is an appropriate approach for application in medicine.

Keywords: Albumin; Chemotherapy; Combination index; Gambogic acid; Synergistic antitumor; nanoparticles.

MeSH terms

  • Antineoplastic Agents*
  • Cell Line, Tumor
  • Doxorubicin / pharmacology
  • Nanocomposites*
  • Nanoparticles*
  • Serum Albumin, Bovine
  • Xanthones* / pharmacology

Substances

  • Antineoplastic Agents
  • Xanthones
  • Serum Albumin, Bovine
  • Doxorubicin
  • gambogic acid