Development of a novel thermal-sensitive multifunctional liposome with antibody conjugation to target EGFR-expressing tumors

Nanomedicine. 2019 Jan;15(1):285-294. doi: 10.1016/j.nano.2018.10.006. Epub 2018 Nov 1.

Abstract

A novel EGFR-targeting, thermal-sensitive multifunctional liposome (TSML) was developed based on manganese-doped magnetism-engineered iron oxide nanoparticles (MnMEIOs) and gold nanorods (AuNRs) for efficient photothermal therapy and magnetic resonance (MR) imaging. An Erbitux-conjugated TSML (Erb-TSML) was encapsulated with doxorubicin and gold nanorods conjugated with manganese-doped magnetism-engineered iron oxide nanoparticles, for theranostic applications of EGFR-positive tumors. The Erb-TSML selectively targeted EGFR-positive tumors and promoted tumor destruction by laser activation. Using confocal microscopy, MR and optical imaging, we demonstrated that Erb-TSML specifically bound to A431 tumor cells. No signs of major morphological damages to the normal tissues were observed in mice treated with Erb-TSML and laser, indicating this theranostic platform protected heart against doxorubicin-induced toxicity to normal tissues. These results indicate that the Erb-TSML may be a promising diagnostic and therapeutic platform for EGFR-overexpressing tumors.

Keywords: AuNR@MnMEIO; Doxorubicin; EGFR; Erbitux; MRI; TSML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / chemistry
  • Antineoplastic Agents, Immunological / pharmacology
  • Apoptosis
  • Cell Proliferation
  • Cetuximab / administration & dosage
  • Cetuximab / chemistry
  • Cetuximab / pharmacology
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • ErbB Receptors / antagonists & inhibitors
  • Gold / chemistry
  • Humans
  • Immunoconjugates / administration & dosage
  • Immunoconjugates / chemistry
  • Immunoconjugates / pharmacology*
  • Lasers*
  • Liposomes / administration & dosage*
  • Liposomes / chemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Magnetite Nanoparticles / administration & dosage*
  • Magnetite Nanoparticles / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanotubes / chemistry*
  • Optical Imaging
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Immunological
  • Immunoconjugates
  • Liposomes
  • Magnetite Nanoparticles
  • Gold
  • Doxorubicin
  • EGFR protein, human
  • ErbB Receptors
  • Cetuximab