In Vitro Hyperspectral Biomarkers of Human Chondrosarcoma Cells in Nanoparticle-mediated Radiosensitization Using Carbon Ions

Overview

Journal Sci Rep

Specialty Science

Date 2023 Sep 9

PMID 37689817

Authors

Mihaela Tudor

Roxana Cristina Popescu

Raluca D Negoita

Antoine Gilbert

Mihaela A Ilisanu

Mihaela Temelie

Anca Dinischiotu

Francois Chevalier

Mona Mihailescu

Diana Iulia Savu

Affiliations

Soon will be listed here.

Abstract

New therapeutic approaches are needed for the management of the highly chemo- and radioresistant chondrosarcoma (CHS). In this work, we used polyethylene glycol-encapsulated iron oxide nanoparticles for the intracellular delivery of the chemotherapeutic doxorubicin (IONP) to augment the cytotoxic effects of carbon ions in comparison to photon radiation therapy. The in vitro biological effects were investigated in SW1353 chondrosarcoma cells focusing on the following parameters: cell survival using clonogenic test, detection of micronuclei (MN) by cytokinesis blocked micronucleus assay and morphology together with spectral fingerprints of nuclei using enhanced dark-field microscopy (EDFM) assembled with a hyperspectral imaging (HI) module. The combination of IONP with ion carbon or photon irradiation increased the lethal effects of irradiation alone in correlation with the induction of MN. Alterations in the hyperspectral images and spectral profiles of nuclei reflected the CHS cell biological modifications following the treatments, highlighting possible new spectroscopic markers of cancer therapy effects. These outcomes showed that the proposed combined treatment is promising in improving CHS radiotherapy.

Citing Articles

Mesenchymal Stem Cells-Derived Small Extracellular Vesicles and Their Validation as a Promising Treatment for Chondrosarcoma in a 3D Model in Vitro.

Romano E, Perut F, Avnet S, Di Pompo G, Silvestri S, Roffo F Biotechnol Bioeng. 2024; 122(3):667-676.

PMID: 39690717 PMC: 11808436. DOI: 10.1002/bit.28909.

Genetics and Molecular Pathogenesis of the Chondrosarcoma: A Review of the Literature.

Iacobescu G, Corlatescu A, Serban B, Spiridonica R, Costin H, Cirstoiu C Curr Issues Mol Biol. 2024; 46(11):12658-12671.

PMID: 39590345 PMC: 11593320. DOI: 10.3390/cimb46110751.

Enhancing Proton Radiosensitivity of Chondrosarcoma Using Nanoparticle-Based Drug Delivery Approaches: A Comparative Study of High- and Low-Energy Protons.

Tudor M, Popescu R, Irimescu I, Rzyanina A, Tarba N, Dinischiotu A Int J Mol Sci. 2024; 25(21).

PMID: 39519034 PMC: 11546389. DOI: 10.3390/ijms252111481.

Specific spectral sub-images for machine learning evaluation of optical differences between carbon ion and X ray radiation effects.

Negoita R, Ilisanu M, Irimescu I, Popescu R, Tudor M, Mihailescu M Heliyon. 2024; 10(15):e35249.

PMID: 39170121 PMC: 11336423. DOI: 10.1016/j.heliyon.2024.e35249.

Unveiling Nanoparticles: Recent Approaches in Studying the Internalization Pattern of Iron Oxide Nanoparticles in Mono- and Multicellular Biological Structures.

Petcov T, Straticiuc M, Iancu D, Mirea D, Trusca R, Mereuta P J Funct Biomater. 2024; 15(6).

PMID: 38921542 PMC: 11204647. DOI: 10.3390/jfb15060169.

References

de Jong Y, Ingola M, Briaire-de Bruijn I, Kruisselbrink A, Venneker S, Palubeckaite I . Radiotherapy resistance in chondrosarcoma cells; a possible correlation with alterations in cell cycle related genes. Clin Sarcoma Res. 2019; 9:9. PMC: 6540537. DOI: 10.1186/s13569-019-0119-0. View

Gelderblom H, Hogendoorn P, Dijkstra S, van Rijswijk C, Krol A, Taminiau A . The clinical approach towards chondrosarcoma. Oncologist. 2008; 13(3):320-9. DOI: 10.1634/theoncologist.2007-0237. View

Gilbert A, Tudor M, Montanari J, Commenchail K, Savu D, Lesueur P . Chondrosarcoma Resistance to Radiation Therapy: Origins and Potential Therapeutic Solutions. Cancers (Basel). 2023; 15(7). PMC: 10093143. DOI: 10.3390/cancers15071962. View

Catanzano A, Kerr D, Lazarides A, Dial B, Lane W, Blazer D . Revisiting the Role of Radiation Therapy in Chondrosarcoma: A National Cancer Database Study. Sarcoma. 2019; 2019:4878512. PMC: 6815626. DOI: 10.1155/2019/4878512. View

Guan X, Gao J, Hu J, Hu W, Yang J, Qiu X . The preliminary results of proton and carbon ion therapy for chordoma and chondrosarcoma of the skull base and cervical spine. Radiat Oncol. 2019; 14(1):206. PMC: 6869181. DOI: 10.1186/s13014-019-1407-9. View

Girard N, Lhuissier E, Aury-Landas J, Cauvard O, Lente M, Boittin M . Heterogeneity of chondrosarcomas response to irradiations with X-rays and carbon ions: A comparative study on five cell lines. J Bone Oncol. 2020; 22:100283. PMC: 7082554. DOI: 10.1016/j.jbo.2020.100283. View

Vares G, Ahire V, Sunada S, Kim E, Sai S, Chevalier F . A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells. Radiother Oncol. 2020; 150:253-261. DOI: 10.1016/j.radonc.2020.07.034. View

Lacombe S, Porcel E, Scifoni E . Particle therapy and nanomedicine: state of art and research perspectives. Cancer Nanotechnol. 2017; 8(1):9. PMC: 5698390. DOI: 10.1186/s12645-017-0029-x. View

Fortuin A, Meijer H, Thompson L, Witjes J, Barentsz J . Ferumoxtran-10 ultrasmall superparamagnetic iron oxide-enhanced diffusion-weighted imaging magnetic resonance imaging for detection of metastases in normal-sized lymph nodes in patients with bladder and prostate cancer: do we enter the era after.... Eur Urol. 2013; 64(6):961-3. DOI: 10.1016/j.eururo.2013.08.017. View

10.

Gong X, Wang F, Huang Y, Lin X, Chen C, Wang F . Magnetic-targeting of polyethylenimine-wrapped iron oxide nanoparticle labeled chondrocytes in a rabbit articular cartilage defect model. RSC Adv. 2022; 8(14):7633-7640. PMC: 9078383. DOI: 10.1039/c7ra12039g. View

11.

Tlemsani C, Larousserie F, De Percin S, Audard V, Hadjadj D, Chen J . Biology and Management of High-Grade Chondrosarcoma: An Update on Targets and Treatment Options. Int J Mol Sci. 2023; 24(2). PMC: 9862566. DOI: 10.3390/ijms24021361. View

12.

Popescu R, Savu D, Dorobantu I, Vasile B, Hosser H, Boldeiu A . Efficient uptake and retention of iron oxide-based nanoparticles in HeLa cells leads to an effective intracellular delivery of doxorubicin. Sci Rep. 2020; 10(1):10530. PMC: 7324358. DOI: 10.1038/s41598-020-67207-y. View

13.

Popescu R, Savu D, Bierbaum M, Grbenicek A, Schneider F, Hosser H . Intracellular Delivery of Doxorubicin by Iron Oxide-Based Nano-Constructs Increases Clonogenic Inactivation of Ionizing Radiation in HeLa Cells. Int J Mol Sci. 2021; 22(13). PMC: 8267614. DOI: 10.3390/ijms22136778. View

14.

Popescu R, Kopatz V, Andronescu E, Savu D, Doerr W . Nanoparticle-Mediated Drug Delivery of Doxorubicin Induces a Differentiated Clonogenic Inactivation in 3D Tumor Spheroids In Vitro. Int J Mol Sci. 2023; 24(3). PMC: 9916819. DOI: 10.3390/ijms24032198. View

15.

Hamdi D, Barbieri S, Chevalier F, Groetz J, Legendre F, Demoor M . In vitro engineering of human 3D chondrosarcoma: a preclinical model relevant for investigations of radiation quality impact. BMC Cancer. 2015; 15:579. PMC: 4529727. DOI: 10.1186/s12885-015-1590-5. View

16.

Ternad I, Penninckx S, Lecomte V, Vangijzegem T, Conrard L, Lucas S . Advances in the Mechanistic Understanding of Iron Oxide Nanoparticles' Radiosensitizing Properties. Nanomaterials (Basel). 2023; 13(1). PMC: 9823929. DOI: 10.3390/nano13010201. View

17.

Aroui S, Brahim S, De Waard M, Kenani A . Cytotoxicity, intracellular distribution and uptake of doxorubicin and doxorubicin coupled to cell-penetrating peptides in different cell lines: a comparative study. Biochem Biophys Res Commun. 2009; 391(1):419-25. DOI: 10.1016/j.bbrc.2009.11.073. View

18.

Heaven C, Wanstall H, Henthorn N, Warmenhoven J, Ingram S, Chadwick A . The suitability of micronuclei as markers of relative biological effect. Mutagenesis. 2022; 37(1):3-12. PMC: 8976228. DOI: 10.1093/mutage/geac001. View

19.

Oike T, Niimi A, Okonogi N, Murata K, Matsumura A, Noda S . Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy. Sci Rep. 2016; 6:22275. PMC: 4772097. DOI: 10.1038/srep22275. View

20.

Wang X, Cui Y, Irudayaraj J . Single-Cell Quantification of Cytosine Modifications by Hyperspectral Dark-Field Imaging. ACS Nano. 2015; 9(12):11924-32. PMC: 4766098. DOI: 10.1021/acsnano.5b04451. View