Bioactive Assembly Cofactor-Assisted Ursolic Acid Helix for Enhanced Anticancer Efficacy via In Situ Virus-like...

Area of Science:

• Nanomedicine
• Biomaterials Science
• Cancer Therapeutics

Background:

• Pentacyclic triterpenoids like ursolic acid (UA) show anticancer potential but suffer from poor solubility and bioavailability.
• Clinical translation of natural anticancer compounds is hindered by formulation and delivery challenges.

Purpose of the Study:

• To develop a novel nanoplatform for enhanced ursolic acid (UA) delivery and efficacy.
• To utilize polypeptoid assembly cofactors for stimuli-responsive nanostructure formation within the tumor microenvironment (TME).

Main Methods:

• Co-assembly of UA with bioactive polypeptoid polyelectrolytes into stimuli-responsive nanostructures.
• Design of acid-responsive and target-specific (lactobionic acid) nanoparticles for TME-triggered release.
• Investigation of intracellular nanoparticle transformation, mitochondrial targeting, and UA release mechanisms.

Main Results:

• The nanoplatform demonstrated pH-responsive transformation from helical fibers to virus-like clusters in the acidic TME, enhancing tumor penetration.
• Intracellular release of UA triggered by thioether bond oxidation led to mitochondrial damage and apoptosis.
• Significant synergistic therapeutic effects were observed, with superior tumor growth suppression and reduced metastasis in vivo compared to individual components.

Conclusions:

• The developed polypeptoid-assisted nanoplatform effectively enhances UA's solubility, bioavailability, and targeted delivery for cancer therapy.
• This synergistic approach offers a promising strategy for leveraging natural compounds in advanced nanomedicine for improved cancer treatment outcomes.