Albumin-Stabilized Metal-Organic Nanoparticles for Effective Delivery of Metal Complex Anticancer Drugs

ACS Appl Mater Interfaces. 2018 Oct 17;10(41):34974-34982. doi: 10.1021/acsami.8b12812. Epub 2018 Oct 4.

Abstract

Many metal-organic complexes showed potent anticancer efficacy, but their clinical applications were limited by the lack of administration route because of their poor solubility. To make metal-organic nanoparticles (MONPs) comprising metal complex drugs is a new formulation strategy for their administration. Herein, we developed a facile synthesis of an MONP composed of bovine serum albumin (BSA), Cu2+, and an anticancer agent, 5-nitro-8-hydroxyquinoline (NQ) with albumin as a nanoreactor. The resultant BSA/Cu/NQ nanoparticle (BSA/Cu/NQ NP) showed good stability in different physiological buffers and could target tumors through the enhanced permeability and retention effect and receptor-mediated cellular uptake. As the BSA/Cu/NQ NP could be readily and efficiently internalized by cancer cells, it showed much higher cytotoxic cancer cells than the NQ + Cu(II) complex and NQ. Therefore, the treatment with BSA/Cu/NQ NP noticeably enhanced the anticancer efficacy without causing systemic toxicity, indicating that such a facile preparation method has great potential to prepare other metal complex nanoparticles for drug delivery.

Keywords: cancer therapy; drug delivery; metal complex drug; metal−organic nanoparticles; nitroxoline.

MeSH terms

  • A549 Cells
  • Animals
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacokinetics
  • Coordination Complexes* / pharmacology
  • Drug Delivery Systems*
  • Female
  • HeLa Cells
  • Humans
  • Metal Nanoparticles* / chemistry
  • Metal Nanoparticles* / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred ICR
  • Neoplasms, Experimental* / drug therapy
  • Neoplasms, Experimental* / metabolism
  • Neoplasms, Experimental* / pathology
  • Nitroquinolines* / chemistry
  • Nitroquinolines* / pharmacokinetics
  • Nitroquinolines* / pharmacology
  • Serum Albumin, Bovine* / chemistry
  • Serum Albumin, Bovine* / pharmacokinetics
  • Serum Albumin, Bovine* / pharmacology

Substances

  • Coordination Complexes
  • Nitroquinolines
  • Serum Albumin, Bovine
  • nitroxoline