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Updated: May 9, 2025
Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
Folic acid-encapsulated silver nitroprusside nanoparticles for targeted therapy in ovarian cancer
Arti Patel1, Swapnali Londhe2, Sanchita Tripathy3
1Applied biology , Indian Institute of Chemical Technology CSIR, Uppal Road, Tarnaka, Hyderabad 500007, AP, Hyderabad, 500007, INDIA.
Abstract:
Ovarian cancer is the most prevalent fatal, gynecological malignancy in women, resulting in poor survival rate (fifth in cancer deaths) due to its asymptomatic nature. Unmet medical challenges for ovarian cancer are associated with several constraints such as poor bioavailability, nonspecificity, and toxicity-related issues. Targeted drug delivery systems may overcome the existing limitations. Utilizing the concept of overexpression of folate receptors (FRs) in ovarian carcinoma, we have designed FRs-targeted drug delivery systems (AgNNPs-FA) by combining silver nitroprusside nanoparticles (AgNNPs) because of their inherent anticancer properties, as established by our group, and folic acid (FA) as targeting agent that attack FRs in this study. Initially, both AgNNPs and AgNNPs-FA were designed and later characterized using several analytical tools such as dynamic light scattering, x-ray diffraction, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, high-performance liquid chromatography, and Fourier transform-infrared spectroscopy, etc. Thein vitrocell viability assay in a Chinese hamster ovary cell line suggests the biocompatible nature of AgNNPs-FA. The targeted anticancer activity of the AgNNPs-FA is established in human ovarian adenocarcinoma (SK-OV-3) via severalin vitroassays and compared with AgNNPs. Allin vitroassays (cell viability assay, thymidine incorporation assay, scratch assay, cell cycle, apoptosis assay, and tunnel assay) in SK-OV-3 andin vivoexperiments (chorioallantoic membrane assay) in fertilized eggs with AgNNPs-FA exhibit more anticancer activity in a targeted fashion than AgNNPs. The plausible mechanisms behind the anticancer activity of the nanoparticles were demonstrated using the ROS assay (DCFDA and DHE staining), JC-1 staining, immunocytochemistry staining (Ki-67), and Western blot analysis. The results altogether support the idea that this targeted drug delivery system could be used as an alternative treatment strategy for ovarian cancer and other cancers with the overexpression of FRs.
Insights
This study developed a novel targeted drug delivery system (AgNNPs-FA) for ovarian cancer, combining silver nanoparticles with folic acid to target folate receptors. The system demonstrated enhanced anticancer efficacy and biocompatibility, offering a promising alternative treatment strategy.
Area of Science:
- Nanotechnology
- Oncology
- Drug Delivery
Background:
- Ovarian cancer is a leading cause of cancer death in women due to its often asymptomatic nature and limited treatment options.
- Existing treatments face challenges like poor bioavailability, lack of specificity, and toxicity, necessitating advanced drug delivery systems.
- Folate receptors (FRs) are overexpressed in many ovarian cancers, presenting a viable target for selective therapies.
Purpose of the Study:
- To design and characterize a novel folate receptor-targeted drug delivery system (AgNNPs-FA) for ovarian cancer.
- To evaluate the anticancer efficacy and biocompatibility of the AgNNPs-FA system.
- To investigate the underlying mechanisms of the targeted anticancer activity.
Main Methods:
- Synthesis and characterization of silver nitroprusside nanoparticles (AgNNPs) and folate-targeted AgNNPs (AgNNPs-FA) using various analytical techniques.
- In vitro evaluation of biocompatibility using Chinese hamster ovary cell lines.
- Assessment of targeted anticancer activity in human ovarian adenocarcinoma (SK-OV-3) cells and in vivo using the chorioallantoic membrane assay, alongside mechanistic studies (ROS, JC-1, Ki-67, Western blot).
Main Results:
- AgNNPs-FA demonstrated biocompatibility in vitro.
- The targeted AgNNPs-FA exhibited significantly enhanced anticancer activity in SK-OV-3 cells compared to non-targeted AgNNPs.
- In vivo studies and mechanistic assays confirmed the targeted efficacy and elucidated the pathways involved in nanoparticle-induced cancer cell death.
Conclusions:
- The developed AgNNPs-FA system effectively targets folate receptors, showing superior anticancer properties for ovarian cancer.
- This targeted drug delivery approach holds potential for overcoming current treatment limitations in ovarian cancer.
- The findings suggest AgNNPs-FA as a promising alternative therapeutic strategy for FR-overexpressing cancers.
