Triple Therapy of HER2+Cancer Using Radiolabeled Multifunctional Iron Oxide Nanoparticles and Alternating Magnetic Field.
By using radio-labeled multifunctional superparamagnetic iron oxide nanoparticles (SPIONs) and an alternating magnetic field (AMF), we carried out targeted hyperthermia, drug delivery, radio-immunotherapy (RIT), and controlled chemotherapy of cancer tumors. We synthesized and characterized Indium-111-labeled, Trastuzumab and Doxorubicin (DOX)-conjugated APTES-PEG-coated SPIONs in our previous work. Then, we evaluated their capability in SPECT/MRI (single photon emission computed tomography/magnetic resonance imaging) dual modal molecular imaging, targeting, and controlled release. In this research, AMF was introduced to evaluate therapeutic effects of magnetic hyperthermia on radionuclide-chemo therapy of HER2+cells and tumor (HER2+)-bearing mice. In vitro and in vivo experiments using synthesized complex were repeated under an AMF (f: 100 KHz, H: 280 Gs). Instead of an intra-tumor injection in most hyperthermia experiments, SPIONs were injected to the tail vein, based on our delivery strategies. For magnetic delivery, we held a permanent Nd-B-Fe magnet near the tumor region. The results showed that simultaneous magnetic hyperthermia enhanced SKBR3 cancer cells, killing by 24%, 28%, 33%, and 80% at 48 hours post-treatment for treated cells with (1) bare SPIONs; (2) antibody-conjugated, DOX-free, surface-modified SPIONs; (3)111In-labeled, antibody-conjugated surface-modified SPIONs; and (4)111In-labeled, antibody- and DOX-conjugated surface-modified SPIONs, respectively. Moreover, tumor volume inhibitory rate was 85% after a 28 day period of treatment. By using this method, multimodal imaging-guided, targeted hyperthermia, RIT, and controlled chemotherapy could be achievable in the near future.
1 Energy Engineering and Physics Faculty, AmirKabir University of Technology , Tehran, Iran .
Hamidreza
H
Zolata
1 Energy Engineering and Physics Faculty, AmirKabir University of Technology , Tehran, Iran .
Hossein
H
Afarideh
2 Rays Application Department, Shahid Beheshti University of Tehran , Tehran, Iran .
Fereydoun Abbasi
FA
Davani
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D005334:Fever / Q000628:therapy*; D006801:Humans; D007205:Indium Radioisotopes / Q000008:administration & dosage / Q000737:chemistry; D055909:Magnetic Field Therapy / Q000379:methods*; D008280:Magnetics / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D016499:Radioimmunotherapy / Q000379:methods; D011897:Random Allocation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D000068878:Trastuzumab / Q000008:administration & dosage / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D004317:Doxorubicin; D005290:Ferric Compounds; D007205:Indium Radioisotopes; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C000499:ferric oxide; C508053:ERBB2 protein, human
HER2+ cancer; controlled chemotherapy superparamagnetic iron oxide nanoparticles; radio-immunotherapy; targeted hyperthermia