Image-Guided Peri-Tumoral Radiofrequency Hyperthermia-Enhanced Direct Chemo-Destruction of Hepatic Tumor Margins

Chen, Minjiang; Zhang, Feng; Shen, Jingjing; Weng, Qiaoyou; Li, Peicheng; Li, Qiang; Qian, Kun; Ji, Hongxiu; Pietrini, Sean D.; Ji, Jiansong; Yang, Xiaoming

doi:10.3389/fonc.2021.593996

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…The VX2 tumor was propagated by the transplanted tumor of the rabbit model, which were left based on our previous research and stored in liquid nitrogen, and the orthotopic models of liver tumors were also established as our previously reports [ 18 , 41 ]. Briefly, 31 male New Zealand white rabbits (2–2.5 kg in weight) were prepared, and one was the donor rabbit and the other thirty were the intervention ones.…”

Section: Methodsmentioning

confidence: 99%

“…Hyperthermia has also been confirmed to improve the anti-tumor efficacy of chemotherapeutic drugs by increasing the delivery efficiency and distribution [ 17 ]. Our previous studies have also shown that radiofrequency hyperthermia can improve the distribution of chemotherapy drugs in the tumor and enhance the killing effect of tumor cells [ 18 ]. Therefore, if hyperthermia can be introduced into the existing chemoembolization treatment system, it will significantly improve the efficacy of TACE treatment.…”

Section: Introductionmentioning

confidence: 99%

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Homogenous multifunctional microspheres induce ferroptosis to promote the anti-hepatocarcinoma effect of chemoembolization

Chen

Gao

et al. 2022

J Nanobiotechnol

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Transcatheter arterial chemoembolization (TACE) is one of the main palliative therapies for advanced hepatocellular carcinoma (HCC), which is also regarded as a promising therapeutic strategy for cancer treatment. However, drug-loaded microspheres (DLMs), as commonly used clinical chemoembolization drugs, still have the problems of uneven particle size and unstable therapeutic efficacy. Herein, gelatin was used as the wall material of the microspheres, and homogenous gelatin microspheres co-loaded with adriamycin and Fe3O4 nanoparticles (ADM/Fe3O4-MS) were further prepared by a high-voltage electrospray technology. The introduction of Fe3O4 nanoparticles into DLMs not only provided excellent T2-weighted magnetic resonance imaging (MRI) properties, but also improved the anti-tumor effectiveness under microwave-induced hyperthermia. The results showed that ADM/Fe3O4-MS plus microwave irradiation had significantly better antitumor efficacy than the other types of microspheres at both cell and animal levels. Our study further confirmed that ferroptosis was involved in the anti-tumor process of ADM/Fe3O4-MS plus microwave irradiation, and ferroptosis marker GPX4 was significantly decreased and ACSL4 was significantly increased, and ferroptosis inhibitors could reverse the tumor cell killing effect caused by ADM/Fe3O4-MS to a certain extent. Our results confirmed that microwave mediated hyperthermia could amplify the antitumor efficacy of ADM/Fe3O4-MS by activating ferroptosis and the introduction of Fe3O4 nanoparticles can significantly improve TACE for HCC. This study confirmed that it was feasible to use uniform-sized gelatin microspheres co-loaded with Fe3O4 nanoparticles and adriamycin to enhance the efficacy of TACE for HCC. Graphical Abstract

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Homogenous multifunctional microspheres induce ferroptosis to promote the anti-hepatocarcinoma effect of chemoembolization

Chen

Gao

et al. 2022

J Nanobiotechnol

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“…CdSe/Fe3O4 nanoplatforms coated with multi-mode polymers had both optical and magnetic functions [128,129]. They co-wrapped with CdSe quantum dots and Fe3O4-NPs, and it was demonstrated for the first time that they may have biomedical applications based on two-photon and magnetothermal therapies such as Extensive studies have shown that thermotherapy is an effective sensitizer of tumor chemoresistancy, which can greatly improve the effectiveness of chemotherapy [130] and enhance the antitumor effect of chemotherapeutic agents [131]. Therefore, the introduction of hyperthermia into the chemoembolization system could significantly improve the efficacy of transcatheter arterial chemoembolization (TACE).…”

Section: Metabolism Modulation By Heat Stressmentioning

confidence: 99%

Progress in the Mechanism of the Effect of Fe3O4 Nanomaterials on Ferroptosis in Tumor Cells

Wang

Bao

et al. 2023

Molecules

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Ferroptosis is a new form of iron-dependent programmed cell death discovered in recent years, which is caused by the accumulation of lipid peroxidation (LPO) and reactive oxygen species (ROS). Recent studies have shown that cellular ferroptosis is closely related to tumor progression, and the induction of ferroptosis is a new means to inhibit tumor growth. Biocompatible Fe3O4 nanoparticles (Fe3O4-NPs), rich in Fe2+ and Fe3+, act as a supplier of iron ions, which not only promote ROS production but also participate in iron metabolism, thus affecting cellular ferroptosis. In addition, Fe3O4-NPs combine with other techniques such as photodynamic therapy (PDT); heat stress and sonodynamic therapy (SDT) can further induce cellular ferroptosis effects, which then enhance the antitumor effects. In this paper, we present the research progress and the mechanism of Fe3O4-NPs to induce ferroptosis in tumor cells from the perspective of related genes and chemotherapeutic drugs, as well as PDT, heat stress, and SDT techniques.

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“…Based on these findings we sought to develop a new approach, to simultaneously deliver oncolytic therapeutics to the tumor periphery during thermal ablation. This novel concept combines RFA-associated RFH, i.e., combining usual thermal ablation with lethal heat (>60°C) destroying tumor cells in the tumor center, with peri-tumoral specific delivery of high-dose oncolytic therapeutics to further kill tumor cells within the difficult to treat periphery of the ablated tumors ( 24 , 25 ). Thus, this innovative synergistic combination could ensure complete eradication of all viable tumor cells in and adjacent to the tumor being treated, while sparing adjacent normal structures.…”

Section: Introductionmentioning

confidence: 99%

Interventional Optical Imaging-Monitored Synergistic Effect of Radio-Frequency Hyperthermia and Oncolytic Immunotherapy

et al. 2022

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PurposeTo develop a new interventional oncology technique using indocyanine green (ICG)-based interventional optical imaging (OI) to monitor the synergistic effect of radiofrequency hyperthermia (RFH)-enhanced oncolytic immunotherapy.Materials and MethodsThis study included (1) optimization of ICG dose and detection time-window for intracellular uptake by VX2 tumor cells; (2) in-vitro confirmation of capability of using ICG-based OI to assess efficacy of RFH-enhanced oncolytic therapy (LTX-401) for VX2 cells; and (3) in-vivo validation of the interventional OI-monitored, intratumoral RFH-enhanced oncolytic immunotherapy using rabbit models with orthotopic liver VX2 tumors. Both in-vitro and in-vivo experiments were divided into four study groups (n=6/group) with different treatments: (1) combination therapy of RFH+LTX-401; (2) RFH alone at 42°C for 30 min; (3) oncolytic therapy with LTX-401; and (4) control with saline. For in-vivo validation, orthotopic hepatic VX2 tumors were treated using a new multi-functional perfusion-thermal radiofrequency ablation electrode, which enabled simultaneous delivery of both LTX-401 and RFH within the tumor and at the tumor margins.ResultsIn in-vitro experiments, taking up of ICG by VX2 cells was linearly increased from 0 μg/mL to 100 μg/mL, while ICG-signal intensity (SI) reached the peak at 24 hours. MTS assay and apoptosis analysis demonstrated the lowest cell viability and highest apoptosis in combination therapy, compared to three monotherapies (P<0.005). In in-vivo experiments, ultrasound imaging detected the smallest relative tumor volume for the combination therapy, compared to other monotherapies (P<0.005). In both in-vitro and in-vivo experiments, ICG-based interventional optical imaging detected a significantly decreased SI in combination therapy (P<0.005), which was confirmed by the “gold standard” optical/X-ray imaging (P<0.05). Pathologic/laboratory examinations further confirmed the significantly decreased cell proliferation with Ki-67 staining, significantly increased apoptotic index with TUNEL assay, and significantly increased quantities of CD8 and CD80 positive cells with immunostaining in the combination therapy group, compared to other three control groups (P<0.005).ConclusionsWe present a new interventional oncology technique, interventional optical imaging-monitored RFH-enhanced oncolytic immunotherapy, which may open new avenues to effectively manage those patients with larger, irregular and unresectable malignancies, not only in liver but also the possibility in other organs.

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Image-Guided Peri-Tumoral Radiofrequency Hyperthermia-Enhanced Direct Chemo-Destruction of Hepatic Tumor Margins

Cited by 4 publications

References 38 publications

Homogenous multifunctional microspheres induce ferroptosis to promote the anti-hepatocarcinoma effect of chemoembolization

Homogenous multifunctional microspheres induce ferroptosis to promote the anti-hepatocarcinoma effect of chemoembolization

Progress in the Mechanism of the Effect of Fe3O4 Nanomaterials on Ferroptosis in Tumor Cells

Interventional Optical Imaging-Monitored Synergistic Effect of Radio-Frequency Hyperthermia and Oncolytic Immunotherapy

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