Albumin/Hyaluronic Acid Gel Nanoparticles Loaded with a Pyrimidine-Based Drug for Potent Anticancer Activity

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• A pyrimidine-based compound (PP) shows promise for colorectal and breast cancers but suffers from low selectivity and poor water solubility.
• Hydrophobic drugs require effective delivery systems to overcome solubility and targeting challenges in cancer therapy.

Purpose of the Study:

• To develop hyaluronic acid-functionalized albumin nanoparticles (PP-HA-BSA-NPs) for targeted delivery of the pyrimidine-based compound (PP).
• To enhance the anticancer efficacy and reduce the toxicity of PP against CD44-overexpressing cancer cells, including triple-negative breast cancer (MDA-MB-231) and colorectal cancer (HCT 116).

Main Methods:

• Fabrication of albumin gel nanoparticles by cross-linking BSA molecules to encapsulate the hydrophobic drug PP.
• Functionalization of nanoparticles with hyaluronic acid (HA) for targeting CD44-overexpressing cancer cells.
• Characterization of nanoparticle size, polydispersity, colloidal stability, encapsulation efficiency, and drug release profiles.

Main Results:

• BSA/HA nanoparticles exhibited mean sizes below 250 nm, low polydispersity, and excellent colloidal stability for 30 days.
• High encapsulation efficiencies (>85%) and sustained drug release were achieved.
• PP-HA-BSA-NPs demonstrated significant anticancer activity, with IC50 drug concentrations resulting in 55% viability for triple-negative breast cancer cells and 23% for colorectal cancer cells.

Conclusions:

• Hyaluronic acid functionalization enhances nanoparticle targeting capabilities for CD44-overexpressing cancer cells.
• The developed PP-HA-BSA-NPs effectively deliver the anticancer drug, retaining its activity while reducing toxicity.
• These targeted nanoparticles show potential for future in vivo studies and clinical applications in treating aggressive cancers.