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Preparation and Characterization of Fe3O4@MTX Magnetic Nanoparticles for Thermochemotherapy of Primary Central Nervous System Lymphoma in vitro and in vivo

Authors Dai X, Yao J, Zhong Y, Li Y, Lu Q, Zhang Y, Tian X, Guo Z, Bai T

Received 15 February 2019

Accepted for publication 13 November 2019

Published 5 December 2019 Volume 2019:14 Pages 9647—9663

DOI https://doi.org/10.2147/IJN.S205456

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Dr Linlin Sun


Xinyu Dai,1 Jingqing Yao,1 Yuejiao Zhong,2 Yuntao Li,3 Qianling Lu,4 Yan Zhang,1 Xue Tian,1 Zhirui Guo,5 Tingting Bai5

1Department of Neurology, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, People’s Republic of China; 2Department of Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210000, People’s Republic of China; 3Department of General Practice, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, People’s Republic of China; 4Department of Neurology, Third Affiliated Hospital of Nanjing Medical University, Nanjing 210000, People’s Republic of China; 5Department of Geratology, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, People’s Republic of China

Correspondence: Yuejiao Zhong
Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Baiziting 42, Nanjing 210009, People’s Republic of China
Email zhongyuejiao2019@163.com
 
Yuntao Li
Department of General Practice, Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing, Jiangsu, People’s Republic of China
Tel/Fax +86 25 5850 9989
Email 18951762737@163.com

Background: Primary central nervous system lymphomas (PCNSL) are extranodal malignant non-Hodgkin lymphomas (NHL) that arise exclusively in central nervous system (CNS). Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype.
Purpose: To evaluate whether nano drug-loading system-mediated magnetic-targeted thermochemotherapy could produce a better therapeutic effect than single chemotherapy while reducing the use of chemotherapeutic drugs.
Methods: Six groups (control, Fe3O4, MTX, Fe3O4@MTX, Fe3O4 with hyperthermia and Fe3O4@MTX with hyperthermia) were set. Tumor cell apoptosis in each treatment group was detected by flow cytometry. Apoptosis-related gene expressions Caspase-3, Bax and Bcl-2 were detected by qPCR and Western blot; intracranial tumor model of PCNSL was established by intracranial injection of OCI-LY18 tumor cells into BALB/c-Nude mice. Magnetic resonance imaging (MRI) was used to monitor tumor progression and H&E staining was used to observe pathological changes of the tumor tissue.
Results: In vitro, compared with chemotherapy alone, apoptosis rate of Fe3O4@MTX mediated thermochemotherapy group was significantly increased, and expression of apoptosis-inducing gene Caspase-3 and Bax were significantly upregulated in OCI-LY18 cells, while expression of apoptosis-inhibiting Bcl-2 gene was significantly downregulated. In vivo, MRI showed successful generation of intracranial tumor, and tumor volume was significantly smaller in combined thermochemotherapy group than in single chemotherapy group. H&E staining result of tumor tissues in each group was consistent with MRI; tumor cells were significantly reduced in thermochemotherapy group. Expression of apoptosis-related gene Caspase-3 and Bax were significantly upregulated in tumor tissues, while expression of Bcl-2 gene was significantly downregulated.
Conclusion: These results demonstrated in vivo and in vitro that the combined thermochemotherapy of Fe3O4@MTX MNPs was superior to the single MTX chemotherapy with less dosage, which may promote apoptosis of DLBCL cells through the mitochondrial apoptotic pathway and provided a new way for the treatment of PCNSL.

Keywords: primary central nervous lymphoma, PCNSL, Fe3O4@MTX magnetic nanoparticles, MNPs, hyperthermia, OCI-LY18 cells


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