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

Abstract

BackgroundPrimary 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.PurposeTo 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.MethodsSix 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.ResultsIn 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.ConclusionThese 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.

Rapid Detection Method for Pathogenic Candida Captured by Magnetic Nanoparticles and Identified Using SERS via AgNPs+

“…After treatment, the residual Candida in the supernatant was counted to calculate the capture rate. 20 The volume of Fe 3 O 4 @PEI (1, 2, 3, 4, and 5 μL) was used as a variable to study the optimal capture efficiency. According to Figure 4 , when the volume of Fe 3 O 4 @PEI ≥ 4 μL, the capture efficiency of Fe 3 O 4 @PEI in the serum samples of different Candida concentrations reached equilibrium.…”

“…This process requires one hour to form Fe 3 O 4 @PEI. 19 , 20 Finally, the Fe 3 O 4 @PEI was washed with ultra-pure water five times to remove excess PEI.…”

Magnetic Solid Nanoparticles and Their Counterparts: Recent Advances towards Cancer Theranostics

“…The drug release from MNPs could present a constant profile (ultimately maintaining a constant concentration for a certain time) or a sigmoidal drug release, reaching a maximum concentration [ 88 ]. The use of MNPs as a chemotherapeutic vehicle has been studied [ 33 ] since the 1980s, and since then different formulations have been described that incorporate drugs such as DOX [ 89 ], paclitaxel (PTX) [ 90 ], and methotrexate (MTX) [ 91 ] as safer and potential alternatives for the treatment of different cancer types.…”

“…Applying an AMF as a stimulus for the activation of the drug-loaded MNPs can create a synergistic cytotoxic effect on cancer, where the sum of the parts (the chemotherapy and the magnetic hyperthermia) can cause a bigger phenotypic effect than the individual treatments, as demonstrated by diverse research groups. For example, for the treatment of primary central nervous system lymphoma (PCNSL), Dai et al [ 91 ] used six experimental groups (control, Fe 3 O 4 , MTX, Fe 3 O 4 @MTX, Fe 3 O 4 with hyperthermia, and Fe 3 O 4 @MTX with hyperthermia) and observed an increase in the apoptosis rate in vitro for the combinatorial treatment when compared to the other groups used. In their in vivo evaluation, the same combination managed to inhibit more the tumor growth when compared to the rest of groups used, as well as managed to decrease the overall tumor cell numbers as measured by H&E staining (hematoxylin and eosin staining).…”

“…In their in vivo evaluation, the same combination managed to inhibit more the tumor growth when compared to the rest of groups used, as well as managed to decrease the overall tumor cell numbers as measured by H&E staining (hematoxylin and eosin staining). Their results highlight the advantages of this dual treatment in oncology [ 91 ]. Other examples are shown in Table 2 , which summarizes other similar studies involving chemotherapeutics with or without the application of magnetic hyperthermia or photothermic conditions.…”