Design and cellular studies of a carbon nanotube-based delivery system for a hybrid platinum-acridine anticancer agent

J Inorg Biochem. 2016 Dec;165:170-180. doi: 10.1016/j.jinorgbio.2016.07.016. Epub 2016 Jul 27.

Abstract

A three-component drug-delivery system has been developed consisting of multi-walled carbon nanotubes (MWCNTs) coated with a non-classical platinum chemotherapeutic agent ([PtCl(NH3)2(L)]Cl (P3A1; L=N-(2-(acridin-9-ylamino)ethyl)-N-methylproprionimidamide) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (DSPE-mPEG). The optimized P3A1-MWCNTs are colloidally stable in physiological solution and deliver more P3A1 into breast cancer cells than treatment with the free drug. Furthermore, P3A1-MWCNTs are cytotoxic to several cell models of breast cancer and induce S-phase cell cycle arrest and non-apoptotic cell death in breast cancer cells. By contrast, free P3A1 induces apoptosis and allows progression to G2/M phase. Photothermal activation of P3A1-MWCNTs to generate mild hyperthermia potentiates their cytotoxicity. These findings suggest that delivery of P3A1 to cancer cells using MWCNTs as a drug carrier may be beneficial for combination cancer chemotherapy and photothermal therapy.

Keywords: Chemotherapy; Cytotoxicity; Drug delivery; Nanoparticle; Photothermal therapy; Triple negative breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acridines* / chemistry
  • Acridines* / pharmacology
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Drug Delivery Systems / methods*
  • Female
  • Humans
  • Hyperthermia, Induced / methods*
  • Nanotubes, Carbon / chemistry*
  • Phototherapy / methods*
  • Platinum* / chemistry
  • Platinum* / pharmacology

Substances

  • Acridines
  • Antineoplastic Agents
  • Nanotubes, Carbon
  • Platinum