Multi-Stimuli-Responsive DOX Released from Magnetosome for Tumor Synergistic Theranostics

Int J Nanomedicine. 2020 Nov 5:15:8623-8639. doi: 10.2147/IJN.S275655. eCollection 2020.

Abstract

Background: To improve responses to tumor microenvironments for achieving a better therapeutic outcome in combination cancer therapy, poly(ε-caprolactone)-SS-poly(methacrylic acid) diblock copolymer (PCL-SS-PMAA) with a disulfide linkage between the hydrophobic and hydrophilic junctions was synthesized.

Materials and methods: Repeating units of PCL and PMAA in PCL-SS-PMAA were controlled and formulated into polymersomes (PSPps). Truncated octahedral Fe3O4 nanoparticles (IONPs) were synthesized and encapsulated to produce IONPs-PSPps NPs and doxorubicin (DOX) was further loaded to produce IONPs-PSPps@DOX NPs for theranostic applications.

Results: IONPs-PSPps NPs remained a superparamagnetic property with a saturation magnetization value of 85 emu⋅gFe3O4 -1 and a relaxivity value of 180 mM-1⋅s-1. Upon exposure to an alternating magnetic field (AMF), IONPs-PSPps NPs increased temperature from 25°C to 54°C within 15 min. Among test groups, the cell apoptosis was greatest in the group exposed to IONPs-PSPps@DOX NPs with AMF and magnet assistance. In vivo T2-weighted magnetic resonance images of A549 tumor-bearing mice also showed highest contrast and greatest tumor suppression in the tumor with AMF and magnet assistance.

Conclusion: IONPs-PSPps@DOX NPs are a potential theranostic agent having multifaceted applications involving magnetic targeting, MRI diagnosis, hyperthermia and chemotherapy.

Keywords: hyperthermia; magnetic resonance imaging; magnetosome; multi-stimuli-responsive copolymer; theranostics.

MeSH terms

  • A549 Cells
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Apoptosis / drug effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacokinetics*
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Humans
  • Magnetic Resonance Imaging
  • Magnetosomes / chemistry*
  • Male
  • Metal Nanoparticles / administration & dosage
  • Metal Nanoparticles / chemistry
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / diagnostic imaging
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy*
  • Polyesters / chemistry
  • Polymethacrylic Acids / chemistry
  • Theranostic Nanomedicine / methods*
  • Tumor Microenvironment / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Polyesters
  • Polymethacrylic Acids
  • polycaprolactone
  • Doxorubicin