High Efficacy in Hyperthermia-associated with Polyphosphate Magnetic Nanoparticles for Oral Cancer Treatment

  • Taboga SR C
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Abstract

Nanotherapy applied to cancer treatment is constantly evolving, and new approaches to current techniques, such as magnetohyperthermia, are being implemented to solve and minimize the limitations of conventional therapeutic strategies. The purpose of this study was to investigate the action of polyphosphate-coated maghemite nanoparticles (MNPs) on oral squamous cell carcinoma. Human oral cancer cells (UM-SCC14A) were incubated with MNPs at various concentrations and subjected to cell proliferation tests (MTT), apoptosis assays and transmission electron image analysis. Viability and apoptotic events were time and dose dependent. These in vitro tests showed that at the intermediate concentration tested there is no significant toxicity, as confirmed by transmission electron microscopy. For this reason this MNPs concentration was chosen for the subsequent in vivo tests. Oral tumor induction was performed by applying the carcinogen DMBA to Syrian hamsters. Animals were then treated by magnetohyperthermia using MNPs. No signs of general clinical symptoms of toxicity or abnormal behavioral reactions were observed. However, animals treated with MNPs and exposed to the alternating magnetic field in the hyperthermia procedure exhibited a significant and time dependent cancer regression, as confirmed by histopathological analyses and immunohistochemistry. Actually, in quantitative terms of the magnetotherapy efficacy involving these polyphosphate-coated MNPs, 100% recovery (12/12) was observed in the oral cancer tumor bearing Syrian hamsters seven days after the treatment with the magnetohyperthermia procedure. Data supports the suggestion that the MNPs-mediated hyperthermia represents a promising strategy for the treatment of oral cancer.

Figures

  • Figure 1: A. X-ray diffractogram of bare MNPs. B. Infrared spectrum of tripolyphosphate functionalized MNPs. C. Transmission electron micrograph of functionalized MNPs. D. Magnetization versus magnetic field plot of the functionalized MNPs.
  • Figure 2: Effect of MNPs on cell proliferation. MTT assay of UM-SCC14A cells after 12 and 24 hours of incubation with MNPs. Data are the mean ± SD. Within graphs, columns with different superscript letters differ significantly (p<0.01).
  • Figure 3: Effect of MNPs on apoptosis. Acridine orange and alumen ferric staining of UM-SCC14A cells analyzed 24 hours post-incubation with or without MNPs. (A-C) Control experiment without MNP incubation. (D-G) Cells incubated with 0.35×1015, (H-K) 0.7×1015 and (L-O) 1.4×1015 particle/mL. Scale bars represent 10 µm. White arrows indicate cells in apoptosis, and red arrows indicate cells in the process of mitosis. (P) Graphic of the rate of apoptosis. Data are the mean ± SD. Within graphs, columns with different superscript letters differ significantly (p<0.001).
  • Figure 4: TEM images of the UM-SCC14A cell line. (A-C) Control cells without MNP-incubation and (D-F) cells incubated with 0.7×1015 particle/ mL for 24 hours. Scale bars represent 500 nm. Black arrows indicate MNPs internalized by eletrolucid vesicles or eletrodense vesicles in the cytoplasm. Red arrows indicate projections of the plasma membrane. GC: Golgi complex. End: eletrodense endosome. ER: endoplasmatic reticulum. Mi: mitochondria. N: nucleus. Nu: nucleolus. V: eletrolucid autophagic vacuole.
  • Table 1: Effect of MNPs and MHT treatment on DMBA-induced oral carcinogenesis in hamsters.
  • Figure 5: Histopathological sample of the right buccal pouch in the (A) Normal, (B) Cancer, (C) MNP, (D) MNP+AMF1 and (E) MNP+AMF7 groups. Tissues were stained by HE. Scale bars represent 20 µm. Epi: epithelium. Krt: keratin.
  • Figure 6: Histological sections subjected to immunocytochemistry for the detection of the cell proliferation marker PCNA. Slides were counterstained with Harris hematoxylin. PCNA immunostaining of epithelial cells in buccal pouch tissue of male hamsters in the (A-C) Normal, (D-F) Cancer, (G-I) MNP, (J-L) MNP+AMF1 and (M-O) MNP+AMF7 groups. Red arrow: marking limited to the basement membrane of epithelium. Black arrow: atypical mitosis and dispersed marking throughout the tissue, with increased PCNA expression. Scale bars represent 10 µm. Epi: epithelium. Krt: keratin layer. Mit: mitosis. (P) Densitometric analysis. Data are the mean ± SD. Within graphs, columns with different superscript letters differ significantly (p<0.05).
  • Figure 7: Immunocytochemical analysis of active caspase-3, counterstained with Harris hematoxylin. Active caspase-3 immunostaining of epithelial cells in buccal pouch tissue of male hamsters in the (A-C) Normal, (D-E) Cancer, (F-G) MNP, (H-J) MNP+AMF1 and (K-L) MNP+AMF7 groups. Cancer and MNP groups exhibit immunostaining limited to the top layer of the epithelium or the islands of keratin (red arrows), whereas the Normal, MNP+AMF1 and MNP+AMF7 groups exhibited, in addition to markings in the aforementioned region of the epithelium, significant markings dispersed in lower layers (black arrows). Scale bars represent 10 µm. Epi: epithelium. Krt: keratin layer. Mit: mitosis. (M) Densitometric analysis. Data are the mean ± SD. Within graphs, columns with different superscript letters differ significantly (p<0.05).

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APA

Taboga SR, C. M. (2014). High Efficacy in Hyperthermia-associated with Polyphosphate Magnetic Nanoparticles for Oral Cancer Treatment. Journal of Nanomedicine & Nanotechnology, 05(03). https://doi.org/10.4172/2157-7439.1000205

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