Small size fullerenol nanoparticles suppress lung metastasis of breast cancer cell by disrupting actin dynamics

Abstract

BackgroundTumor metastasis is the primary cause of mortality in cancer patients. Migratory breast cancer cells in lymphatic and blood vessels seek new sites and form metastatic colonies in the lung and bone, and then these cancer cells often wreak considerable havoc. With advances in nanotechnology, nanomaterials and nanotechnologies are widely applied in tumor therapy. In this paper, small size fullerenol nanoparticles, which are separated by isoelectric focusing electrophoresis (IFE) for discrepancy of isoelectric point (pI), are used in the study of tumor metastasis.ResultsIn this study, the commendable inhibition of tumor metastasis was uncovered by intravenous injection of purified fullerenol fraction with special surface charge and functional groups, which was separated by IFE for discrepancy of pI. By investigating the actin dynamics in several cancer cell lines, we found these small size fullerenol nanoparticles disturbed actin dynamics. Young’s modulus detection and cell migration assays revealed that fullerenol lowered stiffness and restrained migration of breast cancer cells. Filopodia, the main supporting structures of actin bundles, are important for cell motility and adhesion. Scanning electron microscopy showed that fullerenol reduced the number and length of filopodia. Simultaneously, the inhibition of integrin to form clusters on filopodias, which was likely induced by reorganizing of actin cytoskeleton, impacted cancer cell adhesion and motility.ConclusionsWith intravenous injection of these fullerenol nanoparticles, tumor metastasis is well inhibited in vivo. The underlying mechanism most likely to be attributed to the effect of fullerenol nanoparticles on disturbing actin dynamics. With the disordered actin fiber, cell function is varied, including decreased cell stiffness, reduced filopodia formation, and inactivated integrin.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0380-z) contains supplementary material, which is available to authorized users.

Application of atomic force microscopy in cancer research

“…It is of potential value to estimate the effect of anticancer drugs by regulating changes in the morphological and mechanical properties of cancer cells [ 105 – 107 ]. It is generally believed that decreased adhesion of cancer cells is the first step in metastasis.…”

Cancer cells optimize elasticity for efficient migration

“…Many anti-cancer drugs, like chemotherapeutic agents, are purposely designed to target the cytoskeleton and mechanics of cancer to control cell migration and consequently cell metastasis [ 6 , 21 ]. Some studies have shown that treating cells with anti-cancer drugs or nanoparticles regulated the progress and migration of cancer by reducing their stiffness values [ 22 , 23 ], while other investigations are suggesting exactly an inverse relationship, treated cells are stiffer and less invasive and motile compared with the non-treated cells [ 24 , 25 ].…”

“…In the process of metastasis, cell migration is essential to regulate many biological processes required for cancer invasion, and invasive cells are more migratory than non-invasive cells [ 26 – 30 ]. For example, as mentioned earlier, under some treatments, the invasive ability of invasive cancers is reduced along with a reduction in their migratory ability [ 23 , 24 ]. In the context of cell mechanics, force transmission and deformation of cells are influenced by the elasticity of their bodies and are essential for cell migration [ 31 – 33 ].…”

“…7: 200747 [26][27][28][29][30]. For example, as mentioned earlier, under some treatments, the invasive ability of invasive cancers is reduced along with a reduction in their migratory ability [23,24]. In the context of cell mechanics, force transmission and deformation of cells are influenced by the elasticity of their bodies and are essential for cell migration [31][32][33].…”

Biophysical restriction of growth area using a monodispersed gold sphere nanobarrier prolongs the mitotic phase in HeLa cells

“…Interactions between lopodia and nanoparticles have been described in several previous reports. [66][67][68] The growth area surrounding the cell membrane was easily detectable (Fig. 8B) and multiple lopodia interacting with N-AuNSs were observed by cryo-EM ( Fig.…”