Folic acid and ferritin functionalized reduced Iron-based metal-organic frameworks for anticancer therapy

Int J Biol Macromol. 2024 Dec;282(Pt 6):137079. doi: 10.1016/j.ijbiomac.2024.137079. Epub 2024 Oct 29.

Abstract

Anticancer chemotherapies damage normal tissues, and various drug carriers are under consideration to address this issue. Metal-organic frameworks (MOFs) are promising due to their drug-carrying capacity and tunable properties. Target-inspired surface functionalization may further magnify their potential. In this study, we aim to investigate the anticancer activity of reduced iron-based MOFs (RMOFs) functionalized with ferritin and folic acid and loaded with doxorubicin. Successful synthesis and functionalization are confirmed by electron microscopes, Fourier transform infrared spectroscopy and X-ray diffraction. Anticancer activity is evaluated in different tumor cell lines at various doses. Results indicate that the folic acid functionalized and Dox loaded MOF (FADMOF) showed maximum anticancer potential, leaving only 6 % of 4 T1 cells alive at the highest dose. Ferritin and combo MOFs followed closely, while the plain RMOF lagged behind. Furthermore, in HeLa cells, the RMOF showed the best cytotoxicity, reducing cell viability to a mere 30 % at the highest dose. Similarly, in MCF7 cells, theRMOF) showed the best cytotoxicity, reducing cell viability in a dose-dependent manner and to a mere 25 % at the highest dose. Taken together, this study shows that functionalized MOFs have promising anticancer potential across various cancer cell lines. However, loading with doxorubicin reduces their cytotoxicity.

Keywords: Anticancer therapeutic potential; Cancer therapy; Doxorubicin; Functionalized metal-organic frameworks; Stimulus responsive drug carriers.

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Survival* / drug effects
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacology
  • Drug Carriers / chemistry
  • Ferritins* / chemistry
  • Folic Acid* / chemistry
  • HeLa Cells
  • Humans
  • Iron* / chemistry
  • MCF-7 Cells
  • Metal-Organic Frameworks* / chemistry
  • Neoplasms / drug therapy
  • Neoplasms / pathology

Substances

  • Folic Acid
  • Metal-Organic Frameworks
  • Ferritins
  • Doxorubicin
  • Iron
  • Antineoplastic Agents
  • Drug Carriers