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

Department of Cancer Biology, Wake Forest School of Medicine, Winston Salem, NC 27157, USA.
Biomaterials (Impact Factor: 8.56). 04/2012; 33(10):2961-70. DOI: 10.1016/j.biomaterials.2011.12.052
Source: PubMed


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.

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    • "Burke et al. examined whether NPs could overcome the treatment resistance of BCSCs using a model of triple-negative BCSCs. It was observed that BCSCs are sensitive to nanotube-mediated thermal therapy as they lose their proliferative capacity upon thermal ablation and thus show complete tumour regression and long-term survival of mice bearing CSC-driven breast tumours [119]. Sun et al. reported a rationally designed NP delivery system which can efficiently deliver drugs to BCSCs, contributing significantly to the improved anticancer efficacy. "
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    • "The heat sources commonly used are ultrasound, laser-induced heat or radio wave radiation [16]. Hyperthermia in cancer treatment facilitates drug delivery, tumor eradication and it could eventually cause tumor regression if nanotubes are introduced along with thermal therapy [17] [18]. The utilization of heat to treat superficial tumors was described more than 5 millenniums ago in an Egyptian papyrus [19]. "
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    • "The polymeric spheres can protect the drug from adverse external conditions and control its release [8]. Compared with microspheres, NPs have their own superiority over target effect enhancement and abatement of side effects [9]–[10]. Neovessels in tumor are more permeable for nanoparticles under 400–600 nm to pass, which not only can improve the target function but also can lessen the side effects of anti-tumor drugs[11]. "
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