Targeted Drug Delivery Via Human Epidermal Growth Factor Receptor for Sustained Release of Allyl Isothiocyanate

Curr Top Med Chem. 2018;18(14):1252-1260. doi: 10.2174/1568026618666180810150113.

Abstract

In this study, allyl-isothiocyanate (AITC)-loaded Polylactic-Co-Glycolic Acid (PLGA) Nanoparticles (NPs) were prepared for targeting epithelial squamous carcinoma cells using a specific antibody targeting the Epidermal Growth Factor (EGF) receptor overexpressed on the cell membranes. AITC-loaded PLGA NPs showed more effective anticancer properties compared with free AITC, and their cytotoxicity was even more pronounced when the anti-EGFR antibody was covalently attached to the NPs surface. This targeting ability was additionally tested by co-culturing cervical HeLa cells, with very few EGFR on the membranes, and epithelial squamous carcinoma A431 cells, which largely overexpressed EFGR, being observed the specific localization of the antibody-functionalized AITC-loaded PLGA NPs solely in the latter types of cells, whereas non-functionalized NPs were distributed randomly in both cell types in much lesser extents. Thus, our findings support the development of drug delivery strategies that enhances the delivery of anti-cancer natural compounds to tumor tissue, in this case, by targeting specific tumor cell receptors with cell-specific ligands followed by tumor sensitization.

Keywords: Allyl isothiocyanate; Epidermal growth factor; Isothiocyanates; PLGA; Surface modification; Target delivery..

MeSH terms

  • Antibodies, Monoclonal
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Delayed-Action Preparations
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Food Preservatives / administration & dosage
  • Food Preservatives / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Isothiocyanates / administration & dosage*
  • Isothiocyanates / pharmacology*
  • Lactic Acid
  • Nanoparticles
  • Polyethylene Glycols
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Food Preservatives
  • Isothiocyanates
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Polyethylene Glycols
  • allyl isothiocyanate
  • EGFR protein, human
  • ErbB Receptors