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The resistance of breast cancer stem cells to conventional hyperthermia and their sensitivity to nanoparticle-mediated photothermal therapy.

ABSTRACT: Breast tumors contain a small population of tumor initiating stem-like cells, termed breast cancer stem cells (BCSCs). These cells, which are refractory to chemotherapy and radiotherapy, are thought to persist following treatment and drive tumor recurrence. We examined whether BCSCs are similarly resistant to hyperthermic therapy, and whether nanoparticles could be used to overcome this resistance. Using a model of triple-negative breast cancer stem cells, we show that BCSCs are markedly resistant to traditional hyperthermia and become enriched in the surviving cell population following treatment. In contrast, BCSCs are sensitive to nanotube-mediated thermal treatment and lose their long-term proliferative capacity after nanotube-mediated thermal therapy. Moreover, use of this therapy in vivo promotes complete tumor regression and long-term survival of mice bearing cancer stem cell-driven breast tumors. Mechanistically, nanotube thermal therapy promotes rapid membrane permeabilization and necrosis of BCSCs. These data suggest that nanotube-mediated thermal treatment can simultaneously eliminate both the differentiated cells that constitute the bulk of a tumor and the BCSCs that drive tumor growth and recurrence.

SUBMITTER: Burke AR

PROVIDER: S-EPMC3286596 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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The resistance of breast cancer stem cells to conventional hyperthermia and their sensitivity to nanoparticle-mediated photothermal therapy.

Burke Andrew R AR Singh Ravi N RN Carroll David L DL Wood James C S JC D'Agostino Ralph B RB Ajayan Pulickel M PM Torti Frank M FM Torti Suzy V SV

Biomaterials 20120114 10

Breast tumors contain a small population of tumor initiating stem-like cells, termed breast cancer stem cells (BCSCs). These cells, which are refractory to chemotherapy and radiotherapy, are thought to persist following treatment and drive tumor recurrence. We examined whether BCSCs are similarly resistant to hyperthermic therapy, and whether nanoparticles could be used to overcome this resistance. Using a model of triple-negative breast cancer stem cells, we show that BCSCs are markedly resista ...[more]

PMID: 22245557

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Project description:Innovative synthesis routes revolutionized nanomaterial combination and design possibilities resulting in a new generation of fine-tuned nanoparticles featuring exquisite shape and constitution control. However, there is still room for improvement when it comes to the development of multi-functional nanoparticle agents merging a plurality of therapeutic functions to tackle tumors simultaneously by synergic mechanisms. Herein, we report the design of an optimized nanohybrid for cancer tri-therapy featuring a maghemite (γ-Fe2O3) nanoflower-like multicore nanoparticle conceived for efficient magnetic hyperthermia (MHT) and a spiky copper sulfide shell (IONF@CuS) with a high near-infrared (NIR) absorption coefficient suitable for photothermal (PTT) and photodynamic therapy (PDT). Methods: Spiky-like IONF@CuS nanohybrids were obtained through a straightforward and scalable water-based template sacrificial synthesis, which allows the shell shape control by tuning polyvinylpyrrolidone (PVP) concentration. A comprehensive characterization of nanohybrid size, shape and structural properties was carried out by combining complementary TEM, SEM, HR-TEM, EELS, XRD and NTA. The all-in-one therapeutic multi-functionality was assessed on cancer cells and on tumor-bearing nude mice. Results: Tests carried out on IONF@CuS nanohybrid aqueous dispersion demonstrated their impressive efficiency to convert light (conversion coefficient = 42 ± 6 %) and magnetic stimulation (SAR ~ 350 W g-1) into heat as well as to induce concurrent reactive oxygen species (ROS) formation upon laser irradiation. Such capabilities were further confirmed in cellular environment by in vitro tests and at the organism level by in vivo tests in a murine tumor model. Notably, complete tumor regression was obtained for the PTT mode at low Cu concentration. Overall, these results allowed determining windows of applicability for each therapy individually or in combination. Conclusions: Altogether, the obtained data evidence the successful synthesis of a unique tri-therapeutic nanoparticle featuring highly relevant assets for clinical translation such as reduced nanoparticle administered dose, reduced laser power exposure, reduced magnetic field frequency, and the possibility of serial heating cycles and therapy monitoring by photoacoustic (PA) and magnetic resonance imaging (MRI). Furthermore, the integration of the dual heating capability (MHT + PTT) with the PDT insult offers a unique asset to tackle tumors by multiple cytotoxic strategies in order to improve the therapeutic outcome in a broader spectrum of clinical conditions.

Dataset Information

The resistance of breast cancer stem cells to conventional hyperthermia and their sensitivity to nanoparticle-mediated photothermal therapy.

Publications

The resistance of breast cancer stem cells to conventional hyperthermia and their sensitivity to nanoparticle-mediated photothermal therapy.

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