Abstract
AB016. Oligo-fucoidan enhances boronophenylalanine-boron neutron capture therapy therapeutic effect on tumors: studies of boron biodistribution/microdistribution and microbiota in the hamster cheek pouch oral cancer model
Mónica A. Palmieri1, Jessica A. Goldfinger2, Paula Ramos2, Agustina M. Portu2,3, Magdalena Pezzoni2,3, Sergio I. Nemirovsky3,4, Julia Viglietti2, Marcela A. Garabalino2, Emiliano C. C. Pozzi2, Silvia Thorp2, Paula Curotto2, Verónica A. Trivillin2,3, Ignacio Czornenki2, Vanina A. Medina5, Giselle Saint Martin2, Cristina Costa2, Amanda E. Schwint2,3, Andrea Monti Hughes2,3
1Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina;
2Comisión Nacional de Energía Atómica (CNEA), Buenos Aires, Argentina;
3Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina;
4Instituto de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (IQUIBICEN, CONICET-UBA), Buenos Aires, Argentina;
5Instituto de Investigaciones Biomédicas, Universidad Católica Argentina (BIOMED, UCA-CONICET), Buenos Aires, Argentina
Correspondence to: Andrea Monti Hughes, PhD. Comisión Nacional de Energía Atómica (CNEA), General Paz 1499, San Martin, B1650 Villa Maipú, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Email: andre.mh@gmail.com; andreamonti@cnea.gob.ar.
Background: We previously demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA) in the hamster cheek pouch oral cancer model. Oligo-fucoidan is a sulfated polysaccharide isolated from Laminaria japonica with anticancer and immuno-modulatory properties, and proved useful to increase beneficial microbiota in the gut. We showed an enhancement in tumor control when BPA/BNCT was combined with oligo-fucoidan. In the present study, we evaluated the potential mechanisms underlying this effect.
Methods: Hamsters cancerized employing the 8-week protocol were treated with BPA (15.5 mg 10B/kg, four animals) and BPA + oligo-fucoidan (five animals, 200 mg/kg, topical administration in the cancerized pouch the day before and coupled to BPA injection). Animals were sacrificed 3 h post-BPA. Blood, tumor, precancerous tissue, normal pouch, kidney, and liver samples were processed for boron measurements by inductively coupled plasma-optical emission spectrometry (ICP-OES). For boron microdistribution studies in tumors ± oligo-fucoidan, samples were fixed with liquid nitrogen, sectioned, and mounted on polycarbonate nuclear track detector foils. Samples were irradiated with 1013 n/cm2 at the RA-3 nuclear reactor and then chemically etched during 4 min. For microbiota studies, samples at T0 (non-cancerized pouch), at 8 and 12 weeks of cancerization (3 animals) were collected. Bacterial communities were characterized by metagenome amplicon sequencing.
Results: Oligo-fucoidan administration exhibited a slight tendency to increase absolute boron concentration in tumor (28.5±11.9 vs. 22.2±6.7 ppm) and precancerous tissue (23.6±7.8 vs. 17.6±4.9 ppm) (Student’s t-test P<0.05). Oligo-fucoidan altered boron uptake in stroma. Boron uptake and microdistribution in tumor parenchyma is qualitatively similar between groups. Taxonomy-based analysis at phylum level showed that microbiota composition and proportion changed during cancerization.
Conclusions: Oligo-fucoidan could be enhancing BNCT tumor control due to an increase in boron uptake. Ongoing studies are aimed at evaluating BNCT, oligo-fucoidan, and BNCT + oligo-fucoidan effect on the hamster cheek pouch microbiota. Strategies that could select anti-tumor microbiota will surely help to enhance BNCT.
Keywords: Boronophenylalanine-boron neutron capture therapy (BPA-BNCT); oligo-fucoidan; biodistribution; microdistribution; microbiota
Acknowledgments
The authors would like to thank Hi-Q Marine Biotech (Taiwan) for providing oligo-fucoidan.
Funding: This work was supported by the Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (PICT-2019-00523) and salaries and partial funding from National Atomic Energy Commission, Argentina (CNEA), Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina (CONICET), University of Buenos Aires and Hi-Q Marine Biotech (Taiwan).
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tro.amegroups.com/article/view/10.21037/tro-25-ab016/coif). M.A.P. is current the employee of University of Buenos Aires. A.E.S., G.S.M., M.A.P., S.I.N., V.A.M., J.A.G., P.R., A.M.P., M.P., J.V., M.A.G., E.C.C.P., S.T., P.C., V.A.T., S.I.T., C.C., and A.M.H. are current employees of National Atomic Energy Commission, Argentina (CNEA). A.E.S., M.A.P., A.M.P., M.P., S.I.N., V.A.T., and A.M.H. are current employees of Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina (CONICET). M.A.G., J.V., V.A.T., S.I.T., A.E.S., G.S.M., P.R., E.C.C.P., A.M.P., M.P., M.A.P., S.I.N., A.M.H., V.A.M., J.A.G., P.C., and C.C. received grants from Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación. Equipment, drugs, or supplies and travel were provided by Hi-Q Marine Biotech, Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación and CNEA. The authors have no other conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The animal study protocol was approved by the Institutional Review Board National Atomic Energy Commission Animal Care and Use Committee (CICUAL-CNEA, No. 01/year 2015, No. 01/year 2016, No. 02/year 2016, No. 03/year 2018).
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
doi: 10.21037/tro-25-ab016
Cite this abstract as: Palmieri MA, Goldfinger JA, Ramos P, Portu AM, Pezzoni M, Nemirovsky SI, Viglietti J, Garabalino MA, Pozzi ECC, Thorp S, Curotto P, Trivillin VA, Czornenki I, Medina VA, Martin GS, Costa C, Schwint AE, Monti Hughes A. AB016. Oligo-fucoidan enhances boronophenylalanine-boron neutron capture therapy therapeutic effect on tumors: studies of boron biodistribution/microdistribution and microbiota in the hamster cheek pouch oral cancer model. Ther Radiol Oncol 2025;9:AB016.
