Enzyme-mediated dual-targeted-assembly realizes a synergistic anticancer effect

Area of Science:

• Biochemistry
• Materials Science
• Oncology

Background:

• Peptide-based boron complexes are emerging as novel therapeutic agents.
• Targeting multiple cellular components can enhance anticancer efficacy.
• Understanding molecular assembly mechanisms is crucial for drug development.

Purpose of the Study:

• To design and synthesize homochiral-peptide-based boron diketonate complexes.
• To investigate the molecular assembly and targeting capabilities of these complexes in cancer cells.
• To evaluate the synergistic anticancer effects of co-administered stereoisomers.

Main Methods:

• Synthesis of homochiral-peptide-based boron diketonate complexes.
• Co-administration of stereoisomers in cancer cell lines.
• Analysis of molecular assembly via membrane-bonded enzymes.
• Assessment of cancer spheroid toxicity and cell migration inhibition.

Main Results:

• Successful design and synthesis of novel homochiral-peptide-based boron diketonate complexes.
• Co-administration induced molecular assembly targeting both plasma membrane and lysosomes.
• Dual targeting mediated by membrane-bonded enzymes.
• Demonstrated synergistic anticancer effects, including amplified spheroid toxicity and enhanced inhibition of cancer cell migration.

Conclusions:

• Homochiral-peptide-based boron diketonate complexes can self-assemble for dual targeting in cancer cells.
• This dual-targeting strategy potentiates synergistic anticancer effects.
• The findings support the development of peptide-boron complexes for enhanced cancer therapy.