Cinnamaldehyde-Based ROS-Responsive Polymeric Gene Vectors for Efficient Gene Delivery and Tumor Cell Growth...

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Cancer Nanomedicine

Background:

• Reactive oxygen species (ROS)-sensitive polymers are crucial for cancer therapies.
• Tumor microenvironments often have insufficient ROS levels for optimal therapeutic outcomes.

Purpose of the Study:

• To develop a cinnamaldehyde (CA)-based ROS-responsive cationic polymer (PCA) for enhanced gene delivery and cancer therapy.
• To investigate the self-amplifying ROS-generating and self-accelerating degradation mechanisms of PCA.

Main Methods:

• Synthesis of a novel CA-based ROS-responsive cationic polymer (PCA) utilizing a thioacetal linkage.
• Complexation of PCA with the p53 therapeutic gene.
• Evaluation of PCA/p53 complexes for glutathione (GSH) depletion, ROS upregulation, gene transfection, and tumor cell growth inhibition in vitro and in vivo.

Main Results:

• PCA demonstrated efficient GSH depletion and ROS accumulation via released CA, leading to self-accelerating polymer degradation.
• PCA/p53 complexes showed enhanced gene transfection and significant tumor cell growth suppression.
• The synergistic effect of PCA and p53 resulted in potent anti-tumor activity.

Conclusions:

• PCA serves as an effective self-amplifying ROS-responsive polymeric gene vector for cancer therapy.
• The developed polymer offers a promising strategy for overcoming ROS deficiency in the tumor microenvironment.
• This work provides valuable insights into designing advanced polymeric gene delivery systems for cancer treatment.