Boronated protohaemins: synthesis and in vivo antitumour efficacy

Area of Science:

• Biochemistry
• Materials Science
• Oncology

Background:

• Porphyrin macrocycles conjugated with boron-containing polyhedra are explored for cancer treatment.
• The goal is to design photoactive compounds with minimal dark toxicity.

Purpose of the Study:

• To synthesize and evaluate novel carboranyl and monocarbon-carboranyl derivatives of protohaemin IX.
• To assess the efficacy and toxicity of these derivatives in preclinical cancer models.

Main Methods:

• Synthesis of protohaemin IX derivatives using specific activation methods.
• In vitro cytotoxicity assays on cultured mammalian cells.
• In vivo studies using M-1 sarcoma-bearing rats to evaluate photodynamic therapy efficacy and general toxicity.

Main Results:

• Compound 9, a water-soluble derivative, showed no cytotoxicity in vitro and no general toxicity in rats.
• Compound 9 demonstrated dose-dependent photodynamic therapy activity, causing tumor shrinkage in rats after laser irradiation.
• 88.9% of rats treated with compound 9 achieved tumor-free status within 7-14 days, with no recurrence observed for at least 90 days.
• Protohaemin IX alone was ineffective, indicating the importance of boronation for phototoxic activity.

Conclusions:

• Boronated protohaemin IX derivatives, like compound 9, are effective phototoxins for cancer therapy.
• This study presents the first preclinical in vivo efficacy of boronated protohaemin derivatives as phototoxins.
• The findings expand the therapeutic applications of boronated porphyrins beyond boron neutron capture therapy.