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Effective magnetic hyperthermia induced by mitochondria-targeted nanoparticles modified with triphenylphosphonium-containing phospholipid polymers.

ABSTRACT: Magnetic hyperthermia (MHT) is a promising cancer treatment because tumor tissue can be specifically damaged by utilizing the heat generated by nano-heaters such as magnetite nanoparticles (MNPs) under an alternating magnetic field. MNPs are taken up by cancer cells, enabling intracellular MHT. Subcellular localization of MNPs can affect the efficiency of intracellular MHT. In this study, we attempted to improve the therapeutic efficacy of MHT by using mitochondria-targeting MNPs. Mitochondria-targeting MNPs were prepared by the modification of carboxyl phospholipid polymers containing triphenylphosphonium (TPP) moieties that accumulate in mitochondria. The mitochondrial localization of polymer-modified MNPs was supported by transmission electron microscopy observations of murine colon cancer CT26 cells treated with polymer-modified MNPs. In vitro and in vivo MHT using polymer-modified MNPs revealed that the therapeutic effects were enhanced by introducing TPP. Our results indicate the validity of mitochondria targeting in enhancing the therapeutic outcome of MHT. These findings will pave the way for developing a new strategy for the surface design of MNPs and therapeutic strategies for MHT.

SUBMITTER: Kaneko M

PROVIDER: S-EPMC10475774 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Effective magnetic hyperthermia induced by mitochondria-targeted nanoparticles modified with triphenylphosphonium-containing phospholipid polymers.

Kaneko Masahiro M Yamazaki Hiroto H Ono Takahiro T Horie Masanobu M Ito Akira A

Cancer science 20230706 9

Magnetic hyperthermia (MHT) is a promising cancer treatment because tumor tissue can be specifically damaged by utilizing the heat generated by nano-heaters such as magnetite nanoparticles (MNPs) under an alternating magnetic field. MNPs are taken up by cancer cells, enabling intracellular MHT. Subcellular localization of MNPs can affect the efficiency of intracellular MHT. In this study, we attempted to improve the therapeutic efficacy of MHT by using mitochondria-targeting MNPs. Mitochondria-t ...[more]

PMID: 37409483

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Project description:Magnetic resonance (MR) nano-theranostic hyperthermia uses magnetic nanoparticles to target and accumulate at the lesions and generate heat to kill lesion cells directly through hyperthermia or indirectly through thermal activation and control releasing of drugs. Preclinical and translational applications of MR nano-theranostic hyperthermia are currently limited by a few major theoretical difficulties and experimental challenges in in vivo conditions. For example, conventional models for estimating the heat generated and the optimal magnetic nanoparticle sizes for hyperthermia do not accurately reproduce reported in vivo experimental results. In this work, a revised cluster-based model was proposed to predict the specific loss power (SLP) by explicitly considering magnetic nanoparticle aggregation in in vivo conditions. By comparing with the reported experimental results of magnetite Fe3O4 and cobalt ferrite CoFe2O4 magnetic nanoparticles, it is shown that the revised cluster-based model provides a more accurate prediction of the experimental values than the conventional models that assume magnetic nanoparticles act as single units. It also provides a clear physical picture: the aggregation of magnetic nanoparticles increases the cluster magnetic anisotropy while reducing both the cluster domain magnetization and the average magnetic moment, which, in turn, shift the predicted SLP toward a smaller magnetic nanoparticle diameter with lower peak values. As a result, the heating efficiency and the SLP values are decreased. The improvement in the prediction accuracy in in vivo conditions is particularly pronounced when the magnetic nanoparticle diameter is in the range of ~10-20 nm. This happens to be an important size range for MR cancer nano-theranostics, as it exhibits the highest efficacy against both primary and metastatic tumors in vivo. Our studies show that a relatively 20%-25% smaller magnetic nanoparticle diameter should be chosen to reach the maximal heating efficiency in comparison with the optimal size predicted by previous models.

Dataset Information

Effective magnetic hyperthermia induced by mitochondria-targeted nanoparticles modified with triphenylphosphonium-containing phospholipid polymers.

Publications

Effective magnetic hyperthermia induced by mitochondria-targeted nanoparticles modified with triphenylphosphonium-containing phospholipid polymers.

Similar Datasets

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