Esterase-Responsive Floxuridine-Tethered Multifunctional Nanoparticles for Targeted Cancer Therapy

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.