Hyaluronic acid-functionalized MOFs for combined sunitinib and siRNA therapy in renal cell carcinoma

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapy

Background:

• Renal cell carcinoma (RCC) treatment faces challenges due to drug resistance, necessitating advanced drug delivery systems.
• Metal-organic frameworks (MOFs) offer potential as carriers for multidrug combinations and photodynamic therapy.
• Targeted delivery is crucial to overcome resistance and improve therapeutic efficacy in RCC.

Purpose of the Study:

• To develop a nanoscale MOF (PCN-224) for co-delivery of sunitinib and siRNA targeting VEGFR-2 in RCC.
• To enhance tumor targeting and prevent drug leakage using a hyaluronic acid (HA) coating.
• To evaluate the synergistic anti-cancer effects of combined targeted, genetic, and photodynamic therapies.

Main Methods:

• Synthesis of a Zr-based porphyrinic MOF (PCN-224) loaded with sunitinib and siVEGFR-2.
• Coating the MOF with hyaluronic acid (HA) for tumor targeting (CD44 interaction).
• In vitro evaluation of cell viability, apoptosis, and reactive oxygen species (ROS) generation under laser irradiation (660 nm).
• In vivo biosafety assessment through H&E staining of major organs.

Main Results:

• The HA-coated MOF (St/siVEGFR-2@PCN-224@HA) significantly suppressed RCC cell viability and induced apoptosis.
• Laser irradiation amplified the anti-cancer efficacy by generating cytotoxic ROS.
• Histopathological analysis confirmed the biosafety of the nano-system with no observed organ damage.

Conclusions:

• The developed St/siVEGFR-2@PCN-224@HA system provides a promising triple-inhibition strategy for RCC.
• This approach combines targeted therapy, gene therapy (siVEGFR-2), and photodynamic therapy for enhanced anti-cancer outcomes.
• The MOF-based nano-delivery system demonstrates significant potential for overcoming RCC drug resistance and improving treatment efficacy.