Evaluation of apoptotic and anti-metastatic effects by modified mesoporous silica nanoparticles (MSNs) with Zn and NH 2 containing cisplatin on HT-29 cell line

JOURNAL OF NANOPARTICLE RESEARCH(2023)

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摘要
Colorectal cancer ranks third in terms of diagnosis and second concerning cancer-related mortality. The current research is aimed to synthesize cisplatin-loaded mesoporous silica nanoparticles modified with NH 2 and zinc (Zn-MSN-NH 2 -CP) through a sol–gel process and test their cytotoxicity against colon cancer cells in vitro. HT-29 and HUVEC cell lines were grown in supplemented DMEM medium. MTT test was used to determine the cytotoxicity of prepared formulations against normal cells as well as cancer cells. Real-time PCR was utilized to assess the expression of the apoptotic genes in HT-29 treated with CP, Zn-MSN-NH 2 , and Zn-MSN-NH 2 -CP. Necrosis or early and late apoptosis were also evaluated in cancerous cells through the flow method. Physicochemical characteristics of Zn-MSN-NH 2 were assessed by SEM, TEM, DLS, and FT-IR techniques. According to the release profile, surface modification of Zn-MSN-NH 2 -CP resulted in a more regulated CP release. The Zn-MSN-NH 2 -CP was more stable at 4 °C. Cancerous cells were significantly affected by the cytotoxic effects of both CP and Zn-MSN-NH 2 -CP. Zn-MSN-NH 2 could also minimize the toxicity of the unbound drug towards normal cells, while considerably increasing its viability. Compared to the controls, the expression of pro-apoptotic genes was enhanced in cells treated with IC 50 concentrations of Zn-MSN-NH 2 -CP and CP, while the expression of BCL-2 mRNA showed a decline. Flow cytometry findings also revealed a substantial increase in the early and late apoptosis in cells treated with Zn-MSN-NH 2 -CP. These in-vitro findings introduce Zn-MSN-NH 2 as a promising nanocarrier for increasing the bioavailability and anti-cancer efficacy of CP in colon cancer cells. Graphical Abstract
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关键词
mesoporous silica nanoparticles,mesoporous silica,cisplatin,anti-metastatic
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