Development of ROS-responsive amino acid-based poly(ester amide) nanoparticle for anticancer drug delivery.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Research

Background:

• Reactive oxygen species (ROS) are crucial in cellular processes and diseases like cancer.
• Elevated intracellular ROS in cancer cells presents a unique target for drug delivery.
• ROS-responsive biomaterials are vital for targeted biomedical applications.

Purpose of the Study:

• To design and synthesize a novel ROS-responsive polymer, Met-PEA-PEG.
• To develop Met-PEA-PEG based nanoparticles (NP) for targeted drug delivery.
• To evaluate the efficacy of these nanoparticles as a carrier for the anticancer drug gambogic acid (GA).

Main Methods:

• Synthesis and characterization of L-methionine poly(ester amide)-PEG (Met-PEA-PEG) polymer.
• Self-assembly of Met-PEA-PEG into nano-micellar-type nanoparticles (NP).
• Assessment of NP responsiveness to hydrogen peroxide (H₂O₂) and intracellular ROS levels in cancer cells (PC3).
• Loading of gambogic acid (GA) into NP and evaluation of its release kinetics and cytotoxicity against PC3 and HeLa cells.

Main Results:

• Met-PEA-PEG NP demonstrated sensitivity to oxidative environments, with size and morphology changes in H₂O₂.
• Nile Red dye release from NP was dependent on H₂O₂ concentration, indicating controlled release.
• GA-loaded NP (GA-NP) exhibited enhanced cytotoxicity against PC3 and HeLa cancer cells compared to free GA.
• GA-NP induced higher apoptosis and mitochondrial depolarization in PC3 cells than free GA.

Conclusions:

• The novel Met-PEA-PEG NP is responsive to ROS, making it suitable for targeting cancer cells.
• Met-PEA-PEG NP effectively improved the therapeutic effect of gambogic acid.
• These ROS-responsive nanoparticles show potential as a drug delivery system for anticancer therapies.