Rational design of peptides to overcome drug resistance by metabolic regulation

Abstract

Chemotherapy is widely used clinically, however, its efficacy is often compromised by the development of drug resistance, which arises from prolonged administration of drugs or other stimuli. One of the driven causes of drug resistance in tumors or bacterial infections is metabolic reprogramming, which alters mitochondrial metabolism, disrupts metabolic pathways and causes ion imbalance. Bioactive peptide materials, due to their biocompatibility, diverse bioactivities, customizable sequences, and ease of modification, have shown promise in overcoming drug resistance. This review provides an in-depth analysis of metabolic reprogramming and associated microenvironmental changes that contribute to drug resistance in common tumors and bacterial infections, suggesting potential therapeutic targets. Additionally, we explore peptide-based materials for regulating metabolism and their potential synergic effect with other therapies, highlighting the mechanisms by which these peptides reverse drug resistance. Finally, we discuss future perspectives and the clinical challenges in peptide-based treatments, aiming to offer insights for overcoming drug-resistant diseases.