Cytotoxicity Enhancement in Osteosarcoma with Multifunctional I-131 Radiotherapeutic Nanoparticles: In Vitro Three-Dimensional Spheroid Model and Release Kinetics Modeling
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Published:2024-01-29
Issue:3
Volume:29
Page:630
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Marshall Suphalak Khamruang12ORCID, Taweesap Maneerat1, Saelim Boonyisa1, Pachana Verachai1, Benlateh Nadeeya1, Sangangam Sireetorn1, Bumrungsin Achiraya1, Kholo-asae Haswanee1, Wongtechanon Issaree1
Affiliation:
1. Department of Radiology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand 2. Molecular Imaging and Cyclotron Center, Department of Radiology, Division of Nuclear Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
Abstract
This novel radiolabeled chitosan nanoparticle, facilitated with curcumin, increased doxorubicin cytotoxicity and radiosensitivity to MG-63 osteosarcoma cells in a three-dimensional model. Delivery of the anti-epidermal growth factor receptor (EGFR) targeted carboxymethyl chitosan nanoparticles, directly labeled with Na131I (ICED-N), achieved deep tumor penetration in a three-dimensional model. Of three kinetic models, the Higuchi model more closely matched the experimental curve and release profiles. The anti-EGFR targeting resulted in a 513-fold greater targeting efficacy to MG-63 (EGFR+) cells than the control fibroblast (EGFR−) cells. The curcumin-enhanced ICED-N (4 × 0.925 MBq) fractionated-dose regime achieved an 18.3-fold increase in cell cytotoxicity compared to the single-dose (1 × 3.70 MBq) doxorubicin-loaded nanoparticle, and a 13.6-fold increase in cell cytotoxicity compared to the single-dose Na131I nanoparticle. Moreover, the ICED-N fractionated dose increased cells in the G2/M phase 8.78-fold, indicating the cell cycle arrest in the G2/M phase is associated with DNA fragmentation, and the intracellular damage is unable to be repaired. Overall, the results indicate that the fractionated dose was more efficacious than a single dose, and curcumin substantially increased doxorubicin cytotoxicity and amplified osteosarcoma cell radiosensitivity to Na131I.
Funder
Faculty of Medicine, Prince of Songkla University Research and Development Office (RDO), Prince of Songkla University
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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