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In vitro evaluation of hyaluronate-functionalized multi-walled carbon nanotubes containing trigonelline for their
Seyyed Mostafa Gandomi1, Akbar Safipour Afshar2, Masoud Homayouni Tabrizi3
1Department of Biology, Ne.C., Islamic Azad University, Neyshabur, Iran.
Abstract:
Ovarian cancer is a significant cause of gynecological cancer deaths globally, with current treatments having limited effectiveness and notable side effects. Nanocarrier-based targeted drug delivery systems present a promising strategy to enhance treatment outcomes. This study investigates the cytotoxic effects of multi-walled carbon nanotube-hyaluronic acid-trigonelline (MWCNT-HA-TG) nanocarriers (NCs) on the human ovarian cancer cell line A2780 for the first time. The dynamic light scattering (DLS) analysis revealed a Z-average particle size of 121.7 nm with a polydispersity index (PDI) of 0.2990, indicating moderate size heterogeneity. The zeta potential was measured at -25.46 ± 11.24 mV, suggesting a moderately stable colloidal system. Scanning electron microscopy (SEM) demonstrated a highly interconnected network of MWCNTs within the matrix. Fourier-transform infrared (FTIR) spectroscopy identified characteristic peaks for carboxyl, carbonyl, and hydroxyl groups, validating the successful incorporation of HA and TG. The encapsulation efficiency of TG in the NCs was determined to be 88.45% and the cumulative drug release exhibited an initial burst of 15.4% within 3 h, reaching 84.2% by 72 h. The MTT assay's cytotoxicity assessment revealed a concentration-dependent decrease in A2780 cell viability, with an IC50 of 36.11 µg/mL. In contrast, HDF cells showed significantly lower sensitivity (IC50 > 500 µg/mL). Flow cytometry analysis revealed an increase in apoptotic populations in A2780 cells, with significant increases in both early and late apoptosis as the concentration rose from 3.6 µg/mL to 136 µg/mL. Real-time PCR results demonstrated upregulation of caspase-8, caspase-9, and P53 expressions in TG-treated A2780 cells, indicating a concentration-dependent induction of apoptosis. These findings suggest that MWCNT-HA-TG NCs possess selective cytotoxicity against ovarian cancer cells, presenting a promising strategy for targeted cancer therapy.
Insights
This study introduces novel multi-walled carbon nanotube-hyaluronic acid-trigonelline (MWCNT-HA-TG) nanocarriers for ovarian cancer. These nanocarriers show selective toxicity to ovarian cancer cells, offering a promising targeted therapy approach.
Area of Science:
- Biotechnology and Nanomedicine
- Oncology and Cancer Therapeutics
- Materials Science
Background:
- Ovarian cancer remains a leading cause of gynecological cancer mortality worldwide.
- Current ovarian cancer treatments face limitations in efficacy and present significant side effects.
- Nanocarrier-based drug delivery systems offer a promising avenue for improving cancer treatment outcomes through targeted delivery.
Purpose of the Study:
- To investigate the cytotoxic effects of novel multi-walled carbon nanotube-hyaluronic acid-trigonelline (MWCNT-HA-TG) nanocarriers (NCs) on the A2780 human ovarian cancer cell line.
- To characterize the physicochemical properties and drug release profile of the synthesized MWCNT-HA-TG NCs.
- To evaluate the selective cytotoxicity and apoptotic induction mechanism of MWCNT-HA-TG NCs in ovarian cancer cells compared to normal cells.
Main Methods:
- Physicochemical characterization of MWCNT-HA-TG NCs using Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Fourier-Transform Infrared (FTIR) spectroscopy.
- Determination of Trigonelline (TG) encapsulation efficiency and in vitro drug release kinetics.
- Cytotoxicity assessment via MTT assay, flow cytometry for apoptosis analysis, and Real-time PCR for apoptosis-related gene expression (caspase-8, caspase-9, P53).
Main Results:
- MWCNT-HA-TG NCs exhibited a Z-average particle size of 121.7 nm and a zeta potential of -25.46 mV, indicating moderate stability.
- High encapsulation efficiency (88.45%) and sustained drug release (84.2% by 72 h) were observed.
- MWCNT-HA-TG NCs demonstrated selective concentration-dependent cytotoxicity against A2780 ovarian cancer cells (IC50 = 36.11 µg/mL) with minimal toxicity to HDF cells (IC50 > 500 µg/mL).
- Apoptosis induction was confirmed by flow cytometry and significant upregulation of caspase-8, caspase-9, and P53 gene expression in treated cancer cells.
Conclusions:
- MWCNT-HA-TG nanocarriers are successfully synthesized and characterized, showing favorable properties for drug delivery.
- The developed nanocarriers exhibit potent and selective cytotoxicity against human ovarian cancer cells, inducing apoptosis.
- These findings highlight the potential of MWCNT-HA-TG NCs as a promising targeted therapeutic strategy for ovarian cancer treatment.
