Doxorubicin-loaded cell-derived nanovesicles: an alternative targeted approach for anti-tumor therapy

Int J Nanomedicine. 2017 Apr 4:12:2759-2767. doi: 10.2147/IJN.S131786. eCollection 2017.

Abstract

Cell-derived nanovesicles (CDNs) are an emerging class of biological drug delivery systems (DDS) that retain the characteristics of the cells they were derived from, without the need for further surface functionalization. CDNs are also biocompatible, being derived from natural sources and also take advantage of the enhanced permeability and retention effect due to their nanodimensions. Furthermore, CDNs derived from monocytes were shown to have an in vivo targeting effect, accumulating at the tumor site in a previous study conducted in a mouse tumor model. Here, we report a systematic approach pertaining to various loading methods of the chemotherapeutic drug doxorubicin into our CDNs and examine the differential cellular uptake of drug-loaded CDNs in cancerous (HeLa) and healthy (HEK293) cell lines. Lastly, we proved that the addition of doxorubicin-loaded CDNs to the HeLa and HEK293 co-cultures showed a clear discrimination toward cancer cells at the cellular level. Our results further reinforce the intriguing potential of CDNs as an alternative targeted strategy for anticancer therapy.

Keywords: antitumor strategies; antitumor therapy; biomimetic; bionanotechnology; cell targeting; cell-derived nanovesicles; doxorubicin; extracellular vesicles.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Cell Line, Tumor
  • Coculture Techniques
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Drug Delivery Systems / methods*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mice
  • Nanostructures / administration & dosage*
  • Nanostructures / chemistry

Substances

  • Antibiotics, Antineoplastic
  • Doxorubicin