Anilchandra Attaluri1,2, Sri Kamal Kandala2,3, Haoming Zhou2, Michele Wabler2, Theodore L DeWeese2,4, Robert Ivkov2,3,4,5. 1. Department of Mechanical Engineering, School of Science, Engineering, and Technology, The Pennsylvania State University - Harrisburg, Middletown, PA, USA. 2. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3. Department of Mechanical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA. 4. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 5. Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
Abstract
PURPOSE: Tumor volume largely determines the success of local control of borderline resectable and locally advanced pancreatic cancer with current therapy. We hypothesized that a tumor-mass normalized dose of magnetic nanoparticle hyperthermia (MNPH) with alternating magnetic fields (AMFs) reduces the effect of tumor volume for treatment. METHODS: 18 female athymic nude mice bearing subcutaneous MiaPaCa02 human xenograft tumors were treated with MNPH following intratumor injections of 5.5 mg Fe/g tumor of an aqueous suspension of magnetic iron-oxide nanoparticles. Mice were randomly divided into control (n = 5) and treated groups having small (0.15 ± 0.03 cm3, n = 4) or large (0.30 ± 0.06 cm3, n = 5) tumors. We assessed the clinical feasibility of this approach and of pulsed AMF to minimize eddy current heating using a finite-element method to solve a bioheat equation for a human-scale multilayer model. RESULTS: Compared to the control group, both small and large MiaPaCa02 subcutaneous tumors showed statistically significant growth inhibition. Conversely, there was no significant difference in tumor growth between large and small tumors. Both computational and xenograft models demonstrated higher maximum tumor temperatures for large tumors compared to small tumors. Computational modeling demonstrates that pulsed AMF can minimize nonspecific eddy current heating. CONCLUSIONS: MNPH provides an advantage to treat large tumors because the MION dose can be adjusted to increase power. Pulsed AMF, with adjusted treatment time, can enhance MNPH in challenging cases such as low MION dose in the target tissue and/or large patients by minimizing nonspecific eddy current heating without sacrificing thermal dose to the target. Nanoparticle heterogeneity in tumors remains a challenge for continued research.
PURPOSE:Tumor volume largely determines the success of local control of borderline resectable and locally advanced pancreatic cancer with current therapy. We hypothesized that a tumor-mass normalized dose of magnetic nanoparticle hyperthermia (MNPH) with alternating magnetic fields (AMFs) reduces the effect of tumor volume for treatment. METHODS: 18 female athymic nude mice bearing subcutaneous MiaPaCa02human xenograft tumors were treated with MNPH following intratumor injections of 5.5 mg Fe/g tumor of an aqueous suspension of magnetic iron-oxide nanoparticles. Mice were randomly divided into control (n = 5) and treated groups having small (0.15 ± 0.03 cm3, n = 4) or large (0.30 ± 0.06 cm3, n = 5) tumors. We assessed the clinical feasibility of this approach and of pulsed AMF to minimize eddy current heating using a finite-element method to solve a bioheat equation for a human-scale multilayer model. RESULTS: Compared to the control group, both small and large MiaPaCa02 subcutaneous tumors showed statistically significant growth inhibition. Conversely, there was no significant difference in tumor growth between large and small tumors. Both computational and xenograft models demonstrated higher maximum tumor temperatures for large tumors compared to small tumors. Computational modeling demonstrates that pulsed AMF can minimize nonspecific eddy current heating. CONCLUSIONS:MNPH provides an advantage to treat large tumors because the MION dose can be adjusted to increase power. Pulsed AMF, with adjusted treatment time, can enhance MNPH in challenging cases such as low MION dose in the target tissue and/or large patients by minimizing nonspecific eddy current heating without sacrificing thermal dose to the target. Nanoparticle heterogeneity in tumors remains a challenge for continued research.
Authors: Sean Healy; Andris F Bakuzis; Patrick W Goodwill; Anilchandra Attaluri; Jeff W M Bulte; Robert Ivkov Journal: Wiley Interdiscip Rev Nanomed Nanobiotechnol Date: 2022-03-03
Authors: Anirudh Sharma; Erik Cressman; Anilchandra Attaluri; Dara L Kraitchman; Robert Ivkov Journal: Nanomaterials (Basel) Date: 2022-08-12 Impact factor: 5.719
Authors: Lilianne Beola; Valeria Grazú; Yilian Fernández-Afonso; Raluca M Fratila; Marcelo de Las Heras; Jesús M de la Fuente; Lucía Gutiérrez; Laura Asín Journal: ACS Appl Mater Interfaces Date: 2021-03-12 Impact factor: 9.229