Preparation of MnO@poly-(DMAEMA-co-IA)-conjugated Methotrexate Nano-complex for MRI and Radiotherapy of Breast Cancer Application

Overview

Journal MAGMA

Publisher Springer

Date 2023 Apr 19

PMID 37074514

Authors

Saba Ziyaee

Reza Malekzadeh

Marjan Ghorbani

Behnam Nasiri Motlagh

Vahid Asghariazar

Tohid Mortezazadeh

Affiliations

Soon will be listed here.

Abstract

Objective: A novel efficient pH-sensitive targeted magnetic resonance imaging (MRI) contrast agent and innovative radio-sensitizing system were synthesized based on MnO NPs coated with biocompatible poly-dimethyl-amino-ethyl methacrylate-Co-itaconic acid, (DMAEMA-Co-IA) and targeted with methotrexate (MTX).

Materials And Methods: The as-established NPs were fully characterized and evaluated for MRI signal enhancement, relaxivity, in vitro cell targeting, cell toxicity, blood compatibility, and radiotherapy (RT) efficacy.

Results: The targeted NPs MnO@Poly(DMAEMA-Co-IA) and MTX-loaded NPs inhibited MCF-7 cell viability more effectively than free MTX after 24 and 48 h, respectively, with no noticeable toxicity. Additionally, the insignificant hemolytic activity demonstrated their proper hemo-compatibility. T-weighted magnetic resonance imaging was used to distinguish the differential uptake of the produced MnO@Poly(DMAEMA-Co-IA)-MTX NPs in malignant cells compared to normal ones in the presence of high and low MTX receptor cells (MCF-7 and MCF-10A, respectively). In MRI, the produced theranostic NPs displayed pH-responsive contrast enhancement. As shown by in vitro assays, treatment of cells with MnO@Poly(DMAEMA-Co-IA)-MTX NPs prior to radiotherapy in hypoxic conditions significantly enhanced therapeutic efficacy.

Conclusion: We draw the conclusion that using MnO@Poly(DMAEMA-Co-IA)-MTX NPs in MR imaging and combination radiotherapy may be a successful method for imaging and radiation therapy of hypoxia cells.

References

Clarke J, Everest M . Cancer in the mass print media: fear, uncertainty and the medical model. Soc Sci Med. 2006; 62(10):2591-600. DOI: 10.1016/j.socscimed.2005.11.021. View

Armitage E, Barbas C . Metabolomics in cancer biomarker discovery: current trends and future perspectives. J Pharm Biomed Anal. 2013; 87:1-11. DOI: 10.1016/j.jpba.2013.08.041. View

Mortezazadeh T, Gholibegloo E, Alam N, Dehghani S, Haghgoo S, Ghanaati H . Gadolinium (III) oxide nanoparticles coated with folic acid-functionalized poly(β-cyclodextrin-co-pentetic acid) as a biocompatible targeted nano-contrast agent for cancer diagnostic: in vitro and in vivo studies. MAGMA. 2019; 32(4):487-500. DOI: 10.1007/s10334-019-00738-2. View

James M, Gambhir S . A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev. 2012; 92(2):897-965. DOI: 10.1152/physrev.00049.2010. View

Mansouri H, Gholibegloo E, Mortezazadeh T, Yazdi M, Ashouri F, Malekzadeh R . A biocompatible theranostic nanoplatform based on magnetic gadolinium-chelated polycyclodextrin: in vitro and in vivo studies. Carbohydr Polym. 2020; 254:117262. DOI: 10.1016/j.carbpol.2020.117262. View

Mortezazadeh T, Gholibegloo E, Khoobi M, Alam N, Haghgoo S, Mesbahi A . and characteristics of doxorubicin-loaded cyclodextrine-based polyester modified gadolinium oxide nanoparticles: a versatile targeted theranostic system for tumour chemotherapy and molecular resonance imaging. J Drug Target. 2019; 28(5):533-546. DOI: 10.1080/1061186X.2019.1703188. View

Ojeda-Fournier H, Choe K, Mahoney M . Recognizing and interpreting artifacts and pitfalls in MR imaging of the breast. Radiographics. 2008; 27 Suppl 1:S147-64. DOI: 10.1148/rg.27si075516. View

Mittal P, Kalia V, Dua S . Pictorial essay: Susceptibility-weighted imaging in cerebral ischemia. Indian J Radiol Imaging. 2011; 20(4):250-3. PMC: 3056619. DOI: 10.4103/0971-3026.73530. View

Garcia-Hevia L, Banobre-Lopez M, Gallo J . Recent Progress on Manganese-Based Nanostructures as Responsive MRI Contrast Agents. Chemistry. 2018; 25(2):431-441. DOI: 10.1002/chem.201802851. View

10.

Pan D, Schmieder A, Wickline S, Lanza G . Manganese-based MRI contrast agents: past, present and future. Tetrahedron. 2011; 67(44):8431-8444. PMC: 3203535. DOI: 10.1016/j.tet.2011.07.076. View

11.

Song M, Liu T, Shi C, Zhang X, Chen X . Bioconjugated Manganese Dioxide Nanoparticles Enhance Chemotherapy Response by Priming Tumor-Associated Macrophages toward M1-like Phenotype and Attenuating Tumor Hypoxia. ACS Nano. 2015; 10(1):633-647. PMC: 5242343. DOI: 10.1021/acsnano.5b06779. View

12.

Cong C, He Y, Zhao S, Zhang X, Li L, Wang D . Diagnostic and therapeutic nanoenzymes for enhanced chemotherapy and photodynamic therapy. J Mater Chem B. 2021; 9(18):3925-3934. DOI: 10.1039/d0tb02791j. View

13.

Yu W, Huang D, Liu S, Sha Y, Gao F, Liu H . Polymeric Nanoscale Drug Carriers Mediate the Delivery of Methotrexate for Developing Therapeutic Interventions Against Cancer and Rheumatoid Arthritis. Front Oncol. 2020; 10:1734. PMC: 7526065. DOI: 10.3389/fonc.2020.01734. View

14.

Gholibegloo E, Mortezazadeh T, Salehian F, Forootanfar H, Firoozpour L, Foroumadi A . Folic acid decorated magnetic nanosponge: An efficient nanosystem for targeted curcumin delivery and magnetic resonance imaging. J Colloid Interface Sci. 2019; 556:128-139. DOI: 10.1016/j.jcis.2019.08.046. View

15.

Matthiesen S, Jahnke R, Knittler M . A Straightforward Hypoxic Cell Culture Method Suitable for Standard Incubators. Methods Protoc. 2021; 4(2). PMC: 8167595. DOI: 10.3390/mps4020025. View

16.

Wang Z, Zhang Y, Ju E, Liu Z, Cao F, Chen Z . Biomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumors. Nat Commun. 2018; 9(1):3334. PMC: 6102211. DOI: 10.1038/s41467-018-05798-x. View

17.

Asghariazar V, Kadkhodayi M, Mansoori B, Mohammadi A, Baradaran B . Restoration of miR-143 reduces migration and proliferation of bladder cancer cells by regulating signaling pathways involved in EMT. Mol Cell Probes. 2022; 61:101794. DOI: 10.1016/j.mcp.2022.101794. View

18.

Patil D, Phalak G, Mhaske S . Design and synthesis of bio-based UV curable PU acrylate resin from itaconic acid for coating applications. Des Monomers Polym. 2018; 20(1):269-282. PMC: 5812127. DOI: 10.1080/15685551.2016.1231045. View

19.

Moore T, Rodriguez-Lorenzo L, Hirsch V, Balog S, Urban D, Jud C . Nanoparticle colloidal stability in cell culture media and impact on cellular interactions. Chem Soc Rev. 2015; 44(17):6287-6305. DOI: 10.1039/c4cs00487f. View

20.

Allouni Z, Cimpan M, Hol P, Skodvin T, Gjerdet N . Agglomeration and sedimentation of TiO2 nanoparticles in cell culture medium. Colloids Surf B Biointerfaces. 2008; 68(1):83-7. DOI: 10.1016/j.colsurfb.2008.09.014. View