Gold- and Platinum-Peptide Bioconjugates in Cancer Therapy: Recent Advances and Future Directions

Area of Science:

• Medicinal Chemistry
• Nanotechnology
• Bioconjugation Chemistry

Background:

• Metal-based drugs (platinum, gold) are vital chemotherapy agents but face challenges like toxicity and resistance.
• Peptide conjugation offers a strategy to improve drug delivery, targeting, and activation of metal complexes.
• This review focuses on platinum- and gold-peptide bioconjugates, examining directly reactive and redox-activated systems.

Purpose of the Study:

• To critically analyze platinum- and gold-peptide bioconjugates for cancer therapy.
• To review design strategies, conjugation methods, biological activities, and mechanisms of action.
• To assess the impact of peptide conjugation on metal-based anticancer agent properties.

Main Methods:

• Comprehensive literature survey of platinum- and gold-peptide bioconjugates.
• Focus on studies from the past two decades across major scientific databases.
• Analysis of design, conjugation, biological activity, and mechanism of action.

Main Results:

• Pt(II)-peptide conjugates enhance uptake and targeting but not always cytotoxicity; Pt(IV)-peptide conjugates act as prodrugs with efficacy dependent on reduction kinetics.
• Au(I)-peptide conjugates target thiol/selenol proteins, while Au(III) bioconjugates act as redox-activated prodrugs, with peptide conjugation influencing stability and fate.
• Peptide conjugation offers versatility but success hinges on balancing delivery with metal center reactivity and activation.

Conclusions:

• Peptide conjugation is a powerful strategy for optimizing metal-based anticancer drugs.
• Effective metal-peptide bioconjugates require careful design to balance peptide-mediated delivery with metal reactivity.
• Function-guided design is crucial for achieving selectivity and therapeutic benefits in metal-peptide anticancer agents.