Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles

Abstract

Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain). Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension) form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs) with thio-PEG (polyethylene glycol) and thio-glucose, the resulting functionalized GNPs (Glu-GNPs) were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients) was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells’ elevated glucose consumption over normal cells, different starvation periods were screened in order to achieve optimal treatment effects. Cancer cells were then fed using Glu-GNPs followed by X-ray irradiation treatment. For comparison, solid tumor MCF-7 cells (breast cancer cell line) were studied as well. Our irradiation experimental results show that Glu-GNPs are better irradiation sensitizers to treat THP-1 cells than MCF-7 cells, or Glu-GNPs enhance the cancer killing of THP-1 cells 20% more than X-ray irradiation alone and GNP treatment alone. This finding can help oncologists to design therapeutic strategies to target cancer stem cells and cancer metastasis.

Sugar-decorated mesoporous silica nanoparticles as delivery vehicles for the poorly soluble drug celastrol enables targeted induction of apoptosis in cancer cells

“…Glucose-functionalized nanoparticles have indeed previously been reported to show significant increase in cellular uptake as compared to bare nanoparticles [5][6][7].…”

Nanomaterials in Targeting Cancer Stem Cells for Cancer Therapy

“…Using human monocytic cell line derived from acute monocytic leukemia patients as a model (due to its properties are similar to CSCs), and then fed the cells with Glu-Au NPs followed by X-ray irradiation. The experimental results show that Glu-Au NPs enhanced the elimination of human monocytic cells 20% more than X-ray irradiation alone and Au NP treatment alone (Hu et al, 2015). Kouri et al synthesized Au NPs modified with mature miR-182 duplexes [miR-182-based spherical nucleic acids (182-SNAs), Figure 4A] and injected 182-SNAs intravenously to the orthotopic Glioblastoma multiforme (GBM) xenografts.…”

<p>Glucose-coated Berberine Nanodrug for Glioma Therapy through Mitochondrial Pathway</p>

“…36,37 There are some important reports that have supported the glucose-coating nanoparticle as a key driver for GLUT1/3-mediated nanoparticle internalization in the BBB structure or tumor microenvironments. 18,19,21,38 They implied that glucose-coated nanoparticles can be applied for translational medicine in the future. Furthermore, BBR was the potential drug in different brain diseases including brain tumors, 39 traumatic brain injury, 40 brain ischemia etc.…”