Thermosensitive magnetic liposomes for alternating magnetic field-inducible drug delivery in dual targeted brain tumor chemotherapy

Yu Jen Lu, Er Yuan Chuang, Yu Hsin Cheng, T. S. Anilkumar, Huai An Chen, Jyh Ping Chen

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

The nonspecific distribution and non-targeted heating of chemotherapeutic agents in the human body commonly produce adverse side effects during brain cancer management. Even though an external magnetic field can partially gather extracellular magnetic drug carriers near brain tumor, magnetic guidance alone still cannot precisely identify and target either tumors or healthy tissues due to a lack of selectivity. In this study, we successfully developed thermal and magnetic dual-responsive thermosensitive magnetic liposomes (TML), which co-encapsulates Camptosar (CPT-11)and citric acid-coated magnetic Fe 3 O 4 nanoparticles within the aqueous core and surface-conjugated with Cetuximab (CET)for recognizing over-expressed epidermal growth factor receptors on cancer cell surface. This drug carrier system can control the release of encapsulated drug when exposed to a high-frequency alternating magnetic field (AMF)that elevates the temperature of the liposomal membrane and triggers drug release from TML after their selective endocytosis by cancer cells. By detailed characterizing the physico-chemical and biological properties of liposomes, we demonstrated the liposomal formulation is with high biocompatibility and showed no hemolysis in vitro. Enhanced intracellular uptake of TML-CPT-11-CET by human primary glioblastoma cells (U87)also supported targeted delivery through CET-mediated endocytosis. The treatment of TML-CPT-11-CET solutions by AMF in vitro showed rise in solution temperature and enhanced drug release, which enhanced cytotoxicity of CPT-11 toward U87 though cell apoptosis as revealed from flow cytometry analysis of apoptotic cells and Western blot studies of marker proteins. Finally, the in vivo therapeutic efficacy was demonstrated in mice orthotopic xenograft brain tumor model from IVIS and PET/MRI studies.

Original languageEnglish
Pages (from-to)720-733
Number of pages14
JournalChemical Engineering Journal
Volume373
DOIs
Publication statusPublished - Oct 1 2019

Keywords

  • Alternating magnetic field
  • Cetuximab
  • CPT-11
  • Drug delivery
  • Magnetic liposome
  • Thermo-sensitive

ASJC Scopus subject areas

  • Chemistry(all)
  • Environmental Chemistry
  • Chemical Engineering(all)
  • Industrial and Manufacturing Engineering

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