NF-κB hijacking theranostic Pt(ll) complex in cancer therapy

Area of Science:

• Biochemistry
• Oncology
• Medicinal Chemistry

Background:

• Platinum complexes are established anti-cancer agents but suffer from significant side effects due to non-specific damage to healthy cells.
• The limitations of current platinum-based therapies necessitate the development of more targeted and safer anti-cancer drugs.

Purpose of the Study:

• To design and evaluate a novel cyclometalated platinum (II) complex with specificity for the nuclear factor-κB (NF-κB) protein.
• To investigate the potential of this platinum (II) complex to selectively target cancer cells and impair their proliferation with reduced toxicity to normal cells.

Main Methods:

• Design of a cyclometalated platinum (II) complex capable of binding to nuclear factor-κB (NF-κB).
• Utilized colocalization studies in co-culture cell line models to assess cellular uptake and nuclear translocation.
• Evaluated anti-cancer efficacy and side effects in a murine tumor model compared to cisplatin.

Main Results:

• The platinum (II) complex demonstrated upregulated nuclear translocation specifically in cancer cells, not normal cells, by binding to NF-κB.
• Significant impairment of cancer cell proliferation was observed without adverse effects on healthy cells.
• In a murine model, the complex showed superior tumor growth inhibition compared to cisplatin, with notably reduced side effects and kidney damage.

Conclusions:

• The developed NF-κB-binding platinum (II) complex exhibits high specificity for cancer cells, offering a promising therapeutic strategy.
• Hijacking endogenous trans-nuclear proteins like NF-κB represents a viable approach to achieve cancer-cell specificity and improve therapeutic indices.
• This targeted platinum complex holds potential as a next-generation anti-cancer candidate with an enhanced safety profile.