ROS-responsive dimeric prodrug-based nanomedicine targeted therapy for gastric cancer.

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Gastric cancer (GC) poses a significant global health challenge.
• Ursolic acid (UA) shows promise for inhibiting GC but faces limitations due to poor solubility and biocompatibility.
• Overcoming these limitations is crucial for effective GC treatment.

Purpose of the Study:

• To develop an innovative reactive oxygen species (ROS)-sensitive UA dimeric prodrug delivery system.
• To enhance the anti-gastric cancer efficacy of ursolic acid.
• To improve the clinical applicability of UA for cancer therapy.

Main Methods:

• Synthesized a dimeric UA prodrug linked via a ROS-cleavable bond.
• Formulated nanoparticles with a polyethylene glycol (PEG) shell and RGD peptide surface modification.
• Evaluated drug loading, stability, ROS-triggered drug release, and anti-tumor effects in vitro and in vivo.

Main Results:

• Achieved high drug loading (55% w/w) in the dimeric prodrug nanoparticles.
• Demonstrated rapid and selective conversion of the prodrug to UA in response to ROS.
• Showcased enhanced anti-tumor efficacy against gastric cancer in vitro and in vivo models.
• Confirmed improved colloid stability and extended blood circulation due to the PEG shell.
• Observed increased tumor targeting via RGD surface modification.

Conclusions:

• The developed ROS-sensitive UA dimeric prodrug nanoparticles offer a promising strategy for gastric cancer treatment.
• This novel delivery system effectively overcomes UA's solubility and biocompatibility issues.
• The approach holds potential for advancing UA's clinical application in oncology.