Selective mediation of ovarian cancer SKOV3 cells death by pristine carbon quantum dots/Cu2O composite through targeting matrix metalloproteinases, angiogenic cytokines and cytoskeleton

Abstract

It was shown that some nanomaterials may have anticancer properties, but lack of selectivity is one of challenges, let alone selective suppression of cancer growth by regulating the cellular microenvironment. Herein, we demonstrated for the first time that carbon quantum dots/Cu 2 O composite (CQDs/Cu 2 O) selectively inhibited ovarian cancer SKOV3 cells by targeting cellular microenvironment, such as matrix metalloproteinases, angiogenic cytokines and cytoskeleton. The result was showed CQDs/Cu 2 O possessed anticancer properties against SKOV3 cells with IC 50 = 0.85 μg mL −1 , which was approximately 3-fold lower than other tested cancer cells and approximately 12-fold lower than normal cells. Compared with popular anticancer drugs, the IC 50 of CQDs/Cu 2 O was approximately 114-fold and 75-fold lower than the IC 50 of commercial artesunate (ART) and oxaliplatin (OXA). Furthermore, CQDs/Cu 2 O possessed the ability to decrease the expression of MMP-2/9 and induced alterations in the cytoskeleton of SKOV3 cells by disruption of F-actin. It also exhibited stronger antiangiogenic effects than commercial antiangiogenic inhibitor (SU5416) through down-regulating the expression of VEGFR2. In addition, CQDs/Cu 2 O has a vital function on transcriptional regulation of multiple genes in SKOV3 cells, where 495 genes were up-regulated and 756 genes were down-regulated. It is worth noting that CQDs/Cu 2 O also regulated angiogenesis-related genes in SKOV3 cells, such as Maspin and TSP1 gene, to suppress angiogenesis. Therefore, CQDs/Cu 2 O selectively mediated of ovarian cancer SKOV3 cells death mainly through decreasing the expression of MMP-2, MMP-9, F-actin, and VEGFR2, meanwhile CQDs/Cu 2 O caused apoptosis of SKOV3 via S phase cell cycle arrest. These findings reveal a new application for the use of CQDs/Cu 2 O composite as potential therapeutic interventions in ovarian cancer SKOV3 cells.It was shown that some nanomaterials may have anticancer properties, but lack of selectivity is one of challenges, let alone selective suppression of cancer growth by regulating the cellular microenvironment. Herein, we demonstrated for the first time that carbon quantum dots/Cu 2 O composite (CQDs/Cu 2 O) selectively inhibited ovarian cancer SKOV3 cells by targeting cellular microenvironment, such as matrix metalloproteinases, angiogenic cytokines and cytoskeleton. The result was showed CQDs/Cu 2 O possessed anticancer properties against SKOV3 cells with IC 50 = 0.85 μg mL −1 , which was approximately 3-fold lower than other tested cancer cells and approximately 12-fold lower than normal cells. Compared with popular anticancer drugs, the IC 50 of CQDs/Cu 2 O was approximately 114-fold and 75-fold lower than the IC 50 of commercial artesunate (ART) and oxaliplatin (OXA). Furthermore, CQDs/Cu 2 O possessed the ability to decrease the expression of MMP-2/9 and induced alterations in the cytoskeleton of SKOV3 cells by disruption of F-actin. It also exhibited stronger antiangiogenic effects than commercial antiangiogenic inhibitor (SU5416) through down-regulating the expression of VEGFR2. In addition, CQDs/Cu 2 O has a vital function on transcriptional regulation of multiple genes in SKOV3 cells, where 495 genes were up-regulated and 756 genes were down-regulated. It is worth noting that CQDs/Cu 2 O also regulated angiogenesis-related genes in SKOV3 cells, such as Maspin and TSP1 gene, to suppress angiogenesis. Therefore, CQDs/Cu 2 O selectively mediated of ovarian cancer SKOV3 cells death mainly through decreasing the expression of MMP-2, MMP-9, F-actin, and VEGFR2, meanwhile CQDs/Cu 2 O caused apoptosis of SKOV3 via S phase cell cycle arrest. These findings reveal a new application for the use of CQDs/Cu 2 O composite as potential therapeutic interventions in ovarian cancer SKOV3 cells.

Development and application of naturally derived, cost‐effective CQDs with cancer targeting potential

“…In contrast, MCF‐7 cells treated with N‐CQDs for 48 h had a minor rise in G1 phase cell numbers (56 ± 1.4%). While there was a significant decrease in S phase cell numbers (12 ± 0.3%), (Figure 13) (D. Chen et al, 2021; Feng et al, 2020).…”

Magnetic CuFe2O4 with intrinsic protease-like activity inhibited cancer cell proliferation and migration through mediating intracellular proteins

“…Local recurrence and metastasis are considered to be the main causes of treatment failure for ovarian cancer [30] . Inhibiting the proliferation and metastasis of cancer cells have become the key to developing effective drugs and therapies.…”

“…In addition, cytoskeleton maintained the structural integrity of cells also plays an impotent role in the regulation of tumor metastasis [ 29 , 30 ]. Recently, we reported Cu-MOF and CQDs/Cu 2 O with protease-like activities affected cellular microenvironment and induced ovarian cancer SKOV3 cells death through mediating the expression of matrix metalloproteinases, angiogenic cytokines and cytoskeleton [ 30 , 31 ].…”

An insight into recent developments of copper, silver and gold carbon dots: cancer diagnostics and treatment

“…This was due to the increased heat-stability of various substrates involved in cell proliferation and survival, which are part of the ubiquitin-dependent proteasomal degradation pathway. Chen et al (2021) developed a composite of CD and Cu 2 O and investigated its anticancer and antiangiogenic properties in various cancerous and normal cells (Entry-9 of Table 1). This finding demonstrated that CDs/Cu 2 O displayed enhanced sensitivity towards SKOV3 cells in comparison to HeLa, A549, HT-29, HCT116 cancer cells, as well as normal cells.…”