The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model

Abstract

BackgroundLocal hyperthermia of tumor in conjunction with chemotherapy is a promising strategy for cancer treatment. The aim of this study was to evaluate the efficacy of intratumoral delivery of clinically approved magnetic nanoparticles (MNPs) conjugated with doxorubicin to simultaneously induce magnetic hyperthermia and drug delivery in a hepatocellular carcinoma (HCC) model.Materials and methodsHCC cells expressing luciferase were implanted into the flank of BALB/c-nu mice (n = 19). When the tumor diameter reached 7–8 mm, the animals were divided into four groups according to the injected agents: group A (normal saline, n = 4), group B (doxorubicin, n = 5), group C (MNP, n = 5), and group D (MNP/doxorubicin complex, n = 5). Animals were exposed to an alternating magnetic field (AMF) to receive magnetic hyperthermia, and intratumoral temperature changes were measured.Bioluminescence imagings (BLIs) were performed before treatment and at 3, 7, and 14 days after treatment to measure the tumoral activities. The relative signal intensity (RSI) of each tumor was calculated by dividing the BLI signal at each time point by the value measured before treatment. At day 14 post-treatment, all tumor tissues were harvested to assess the apoptosis rates by pathological examination.ResultsThe rise in temperature of the tumors was 1.88 ± 0.21°C in group A, 0.96 ± 1.05°C in B, 7.93 ± 1.99°C in C, and 8.95 ± 1.31°C in D. The RSI of the tumors at day 14 post-treatment was significantly lower in group D (0.31 ± 0.20) than in group A (2.23 ± 1.14), B (0.94 ± 0.47), and C (1.02 ± 0.21). The apoptosis rates of the tumors were 11.52 ± 3.10% in group A, 23.0 ± 7.68% in B, 25.4 ± 3.36% in C, and 39.0 ± 13.2% in D, respectively.ConclusionsThe intratumoral injection of ferucarbotran conjugated with doxorubicin shows an improved therapeutic effect compared with doxorubicin or ferucarbotran alone when the complex is injected into HCC tissues exposed to AMF for magnetic hyperthermia. This strategy of combining doxorubicin and MNP-induced magnetic hyperthermia exhibits a synergic effect on inhibiting tumor growth in an HCC model.

Hyperthermia mediated by dextran-coated La0.7Sr0.3MnO3 nanoparticles: in vivo studies

“…2 Hyperthermia or heat therapy (typically to the tune of 41°C-47°C) is a promising strategy to combat cancers. 3 Tumor tissues are reported to be more susceptible to high temperatures as compared to normal tissues due to impaired heat dissipation. 4,5 Thus, hyperthermia can destroy the tumor tissues while sparing the healthy ones.…”

Maghemite (γ-Fe2O3) and γ-Fe2O3-TiO2 Nanoparticles for Magnetic Hyperthermia Applications: Synthesis, Characterization and Heating Efficiency

“…This is chiefly due to their excellent intrinsic magnetic properties, ultrasmall nanometer dimensions (5–15 nm) and their ability for dissipating heat using an alternating magnetic field (AMF). In particular, ferrites (mainly magnetite (Fe 3 O 4 ) or maghemite (γ-Fe 2 O 3 )) are very promising materials for MFH and have been effectively utilized for cancer hyperthermia therapy [ 4 , 5 , 6 ]. Furthermore, a combination of iron-based nanoprobes with other transition metals (i.e., Ti, Au, Ag) at the nanoscale lead to formation of bifunctional materials which benefits from the unique properties of both components.…”

Temperature-dependent and time-dependent effects of hyperthermia mediated by dextran-coated La0.7Sr0.3MnO3: in vitro studies

“…1 These high temperatures are reported to kill cancerous cells selectively and are thus useful in treating several types of cancer. [2][3][4] This effect is because of irregular and poor blood flow in the tumor that allows slow dissipation of heat, making cancerous cells more thermosensitive than normal cells.…”