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Silver nanoparticle-embedded graphene oxide-methotrexate for targeted cancer treatment
Raj Kumar Thapa1, Jae Hee Kim1, Jee-Heon Jeong1
1College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, Republic of Korea.
Abstract:
Combination therapies are widely investigated cancer treatment modalities. Carbon based systems such as graphene oxide (GO), plasmonic nanoparticles such as silver nanoparticles (AgNPs), and the folate analog, methotrexate (MTX), have been separately studied for their potential anticancer effects. In this study, we combined these systems to develop AgNPs-embedded GO with conjugated MTX (MTX-GO/AgNPs) and studied their folate receptor-targeted anticancer effects. Results revealed successful formation of AgNPs on GO along with MTX conjugation as suggested by UV/visible, TEM, AFM, FTIR, and XRD analysis. Folate receptor-positive MCF-7 cells were more prone to cytotoxic effects of MTX-GO/AgNPs compared to folate receptor-negative HepG2 cells. Folic acid analog MTX interacts with folate receptors expressed in MCF-7 cells, improving cellular uptake and subsequent anticancer effects of the system. Importantly, AgNPs enhanced the total ROS production within the treated cells leading to improve cellular apoptosis, as evidenced by western blot. Moreover, near infrared (NIR)-induced photothermal effects of GO improved the anticancer activity of the system. Therefore, the combinational therapy system MTX-GO/AgNPs can be potentially applied for effective folate receptor-targeted treatment of cancers.
Insights
This study developed a novel combination therapy using silver nanoparticles embedded in graphene oxide with methotrexate (MTX-GO/AgNPs) for targeted cancer treatment. The MTX-GO/AgNPs system effectively targeted folate receptor-positive cancer cells, enhancing efficacy through photothermal and ROS-mediated apoptosis.
Area of Science:
- Nanotechnology
- Materials Science
- Oncology
Background:
- Combination therapies are crucial for cancer treatment.
- Graphene oxide (GO), silver nanoparticles (AgNPs), and methotrexate (MTX) show individual anticancer potential.
- Targeted drug delivery systems are needed to improve therapeutic efficacy and reduce side effects.
Purpose of the Study:
- To develop and evaluate a novel combination therapy system (MTX-GO/AgNPs) for folate receptor-targeted cancer treatment.
- To investigate the synergistic anticancer effects of AgNPs, GO, and MTX.
- To assess the role of folate receptor targeting in cellular uptake and cytotoxicity.
Main Methods:
- Synthesis of AgNPs-embedded GO with conjugated MTX (MTX-GO/AgNPs).
- Characterization using UV/visible, TEM, AFM, FTIR, and XRD.
- Evaluation of cytotoxicity in folate receptor-positive (MCF-7) and negative (HepG2) cancer cells.
- Assessment of reactive oxygen species (ROS) production and apoptosis via western blot.
- Investigation of near-infrared (NIR) induced photothermal effects.
Main Results:
- Successful synthesis and characterization of MTX-GO/AgNPs.
- Enhanced cytotoxicity in folate receptor-positive MCF-7 cells compared to HepG2 cells.
- MTX-GO/AgNPs increased cellular uptake via folate receptor interaction.
- AgNPs boosted ROS production, leading to increased apoptosis.
- NIR-induced photothermal effect of GO further enhanced anticancer activity.
Conclusions:
- The MTX-GO/AgNPs system demonstrates effective folate receptor-targeted anticancer therapy.
- The combination therapy exhibits synergistic effects through enhanced ROS production and photothermal activity.
- This novel nanoplatform holds promise for developing advanced cancer treatments.
