Inhibition of cancer cell migration with CuS@mSiO₂-PEG nanoparticles by repressing MMP-2/MMP-9 expression

Abstract

The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO 2 -PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study. Using CuS@mSiO 2 -PEG NP stimulation and a transwell migration assay, we found that the migration of HeLa cells was significantly decreased. This phenomenon may be associated with two classical proteins in metastasis: matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). In addition, the mechanism may closely associate with non-receptor tyrosine kinase protein (SRC)/focal adhesion kinase (FAK) signaling pathway which varies in vivo and in vitro. To confirm the differences in the expression of SRC and FAK, related inhibitors were studied for additional comparison. Also, the results indicated that even though the migration inhibition was closely related to SRC and FAK signaling pathway, there may be another unknown regulation mechanism existing and its metastasis inhibition was significant. Confirmed by long-term survival curve study, CuS@mSiO 2 -PEG NPs significantly reduced the metastasis of cancer cells and improved the survival rates of metastasis in a mouse model. Thus, we believe that the direct influence of NPs on cancer cell metastasis is a promising study topic.

Serum amyloid a, a potential biomarker both in serum and tissue, correlates with ovarian cancer progression

“…4b-d). O'Hara R, and Tamamoto T et al had reported that SAA was involved in adhesion, migration, and tissue infiltration of inflammatory cells, induced matrix metalloproteinases which could interact with degrading extracellular matrix (ECM) controlling the diffusion and migration of cells [30][31][32][33][34][35]. Possible mechanisms of SAA for stimulating MMP-9 might be via formyl peptide receptor like-1-mediated signaling [36,37].…”

Serum amyloid a, a potential biomarker both in serum and tissue, correlates with ovarian cancer progression

“…4b-d). O'Hara R, and Tamamoto T et al had reported that SAA was involved in adhesion, migration, and tissue in ltration of in ammatory cells, induced matrix metalloproteinases which could interact with degrading extracellular matrix (ECM) controlling the diffusion and migration of cells [25][26][27][28][29][30]. Possible mechanisms of SAA for stimulating MMP-9 might be via formyl peptide receptor like-1-mediated signaling [31].…”

Harnessing nanomedicine to overcome the immunosuppressive tumor microenvironment

“…For example, Wang et al created copper monosulfide nanocrystals modified with mesoporous silica and PEGylation (CuS@mSiO 2 -PEG). They found a reduction in the metastasis of cancer cells and improved survival rates after subcutaneous injections of HeLa cells that were prestimulated with Cus@mSiO 2 -PEG NPs in comparison with those of cells that were prestimulated with free copper in a HeLa lung metastasis model [138], demonstrating that NPs enhance therapeutic efficacy. Further studies have focused on a new target enzyme candidate, lysyl oxidase (LOX), which is elevated in the TME.…”

“…Accordingly, MMPs have been investigated for preventing and treating tumors; however, the delivery of MMP inhibitors has been challenging due to poor specificity. Recent studies have shown the use of NPs with potential MMP inhibitors to control metastasis in cancer therapy [138,139]. For example, Wang et al created copper monosulfide nanocrystals modified with mesoporous silica and PEGylation (CuS@mSiO 2 -PEG).…”