Related Experiment Video
Updated: Jun 14, 2025
Author Spotlight: Innovative Cancer Therapies with Iron Oxide Nanoparticles for Glioblastoma Treatment
Published on: September 27, 2024
Esterase-Responsive Floxuridine-Tethered Multifunctional Nanoparticles for Targeted Cancer Therapy
Anusree Krishna1, Gowtham Raj1, Sandhya P1
1School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram, Thiruvananthapuram 695551, Kerala India.
Abstract:
Floxuridine is a potential clinical anticancer drug for the treatment of various cancers. However, floxuridine typically causes unfavorable side effects due to its very poor tumor selectivity, and, hence, there is a high demand for the development of novel approaches that permit the targeted delivery of floxuridine into cancerous cells. Herein, the design and synthesis of an esterase-responsive multifunctional nanoformulation for the targeted delivery of floxuridine in esterase-overexpressed cancer cells is reported. Photopolymerization of floxuridine-tethered lipoic acid results in the formation of amphiphilic floxuridine-tethered poly(disulfide). Self-assembly of the amphiphilic polymer results in the formation of nanoparticles with floxuridine decorated on the surfaces of the particles. Integration of aptamer DNA for nucleolin onto the surface of the nanoparticle is demonstrated by exploring the base-pairing interaction of floxuridine with adenine. Targeted internalization of the aptamer-decorated nanoparticle into nucleolin-expressed cancer cells is demonstrated. Esterase triggered cleavage of the ester bond connecting floxuridine with the polymer backbone, and the subsequent targeted delivery of floxuridine into cancer cells is also shown. Excellent therapeutic efficacy is observed both in vitro and also in the 3D tumor spheroid model. This noncovalent strategy provides a simple yet effective strategy for the targeted delivery of floxuridine into cancer cells in a less laborious fashion.
Insights
Researchers developed a novel nanoformulation for targeted delivery of the anticancer drug floxuridine. This approach enhances drug efficacy in cancer cells by improving tumor selectivity and reducing side effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Drug Delivery
Background:
- Floxuridine is a promising anticancer drug with limitations due to poor tumor selectivity and side effects.
- Targeted drug delivery systems are crucial for enhancing anticancer efficacy and minimizing toxicity.
Purpose of the Study:
- To design and synthesize an esterase-responsive nanoformulation for targeted floxuridine delivery to cancer cells.
- To improve the therapeutic efficacy of floxuridine by enhancing its selectivity for cancer cells.
Main Methods:
- Synthesis of amphiphilic floxuridine-tethered poly(disulfide) via photopolymerization.
- Self-assembly of polymers into nanoparticles with surface-conjugated aptamer DNA for nucleolin targeting.
- Demonstration of targeted cellular uptake and esterase-triggered drug release in cancer cells.
Main Results:
- Successful formation of aptamer-decorated nanoparticles capable of targeted internalization into nucleolin-expressing cancer cells.
- Esterase-triggered cleavage of the polymer backbone released floxuridine intracellularly.
- Significant therapeutic efficacy observed in vitro and in 3D tumor spheroid models.
Conclusions:
- The developed nanoformulation enables efficient and targeted delivery of floxuridine to cancer cells.
- This strategy offers a simple, effective, and less laborious approach for improving anticancer therapy.
- The esterase-responsive system holds potential for clinical applications in cancer treatment.
