A size-shrinkable nanoparticle-based combined anti-tumor and anti-inflammatory strategy for enhanced cancer therapy

Area of Science:

• Oncology
• Nanotechnology
• Pharmacology

Background:

• Cancer-related inflammation fuels tumor progression and metastasis.
• Metformin (MET) inhibits nuclear factor-κB (NF-κB), a key inflammatory mediator, but faces limitations in half-life and tumor targeting.
• Targeting cancer-related inflammation is crucial for enhancing cancer therapy.

Purpose of the Study:

• To develop a nanoparticle-based drug delivery system for combined anti-cancer and anti-inflammatory therapy.
• To improve the tumor targeting and efficacy of metformin and doxorubicin.
• To investigate the therapeutic potential of RGD-DGL-GNP nanoparticles loaded with MET and DOX.

Main Methods:

• Loading metformin (MET) and doxorubicin (DOX) onto size-shrinkable RGD-DGL-GNP nanoparticles using pH-sensitive imine bonds.
• Developing RGD-MET-DGL-GNP (RMDG) and RGD-DOX-DGL-GNP (RDDG) nanoparticles for targeted delivery.
• Evaluating the anti-inflammatory effects by measuring NF-κB activity, TNF-α, and IL-6.
• Assessing therapeutic efficacy in xenograft tumor models and pulmonary metastasis models.

Main Results:

• RMDG NPs effectively delivered MET into tumors, inhibiting NF-κB activity and reducing TNF-α and IL-6 levels.
• Nanoparticle co-administration suppressed tumor cell proliferation and demonstrated improved therapeutic effects.
• Combined RDDG and RMDG NPs showed significant efficacy in both tumor growth and metastasis models.

Conclusions:

• Simultaneously targeting tumors and cancer-related inflammation with RDDG and RMDG NPs is a potent anti-cancer strategy.
• The developed nanoparticle system enhances drug delivery and therapeutic outcomes for combination cancer therapy.
• This approach offers a promising avenue for overcoming the limitations of existing cancer treatments.