Doxorubicin-Loaded Core-Shell UiO-66@SiO₂ Metal-Organic Frameworks for Targeted Cellular Uptake and Cancer Treatment

Area of Science:

• Materials Science
• Nanotechnology
• Biomedical Engineering

Background:

• Metal-organic frameworks (MOFs) like UiO-66 offer high capacity for drug delivery but require improved stability and targeting.
• Mesoporous silica (SiO2) coatings can enhance nanoparticle stability and allow surface functionalization.
• Folic acid (FA) conjugation targets cancer cells overexpressing folate receptors, improving drug specificity.

Purpose of the Study:

• To develop a core-shell nanoparticle, UiO-66@SiO2/F127-FA, for targeted delivery of doxorubicin (DOX) in cancer treatment.
• To investigate the effect of silica shell thickness on nanoparticle properties and drug loading.
• To evaluate the in vitro efficacy and cellular uptake of the targeted nanoparticles.

Main Methods:

• Synthesis of core-shell UiO-66@SiO2 nanoparticles with varying silica shell thicknesses.
• Encapsulation of doxorubicin (DOX) into both uncoated and silica-coated nanoparticles.
• Functionalization of nanoparticles with folate-conjugated pluronic F127 (F127-FA).
• Characterization of nanoparticle properties, including colloidal stability, drug loading, and release kinetics.
• In vitro evaluation of cellular uptake and antitumor activity in MCF-7 (cancer) and RAW 264.7 (macrophage) cell lines.

Main Results:

• Silica coating improved colloidal stability and enabled surface functionalization without compromising doxorubicin loading capacity (5.6 wt%).
• Silanization duration influenced silica shell thickness non-linearly due to silicon penetration into the MOF structure.
• Folate conjugation enhanced targeted uptake in folate-receptor-overexpressing MCF-7 cells compared to RAW 264.7 cells.
• DOX-loaded UiO-66@SiO2/F127-FA nanoparticles demonstrated significant in vitro antitumor activity.

Conclusions:

• The developed UiO-66@SiO2/F127-FA core-shell nanoparticles represent a promising drug delivery system for targeted cancer therapy.
• The combination of MOF, silica coating, and folate targeting enhances drug delivery efficiency and specificity.
• This platform offers potential for increased practical value of MOFs in small molecule drug delivery applications.