Doxorubicin conjugates: a practical approach for its cardiotoxicity alleviation

Expert Opin Drug Deliv. 2024 Mar;21(3):399-422. doi: 10.1080/17425247.2024.2343882. Epub 2024 Apr 21.

Abstract

Introduction: Doxorubicin (DOX) emerges as a cornerstone in the arsenal of potent chemotherapeutic agents. Yet, the clinical deployment of DOX is tarnished by its proclivity to induce severe cardiotoxic effects, culminating in heart failure and other consequential morbidities. In response, a panoply of strategies has undergone rigorous exploration over recent decades, all aimed at attenuating DOX's cardiotoxic impact. The advent of encapsulating DOX within lipidic or polymeric nanocarriers has yielded a dual triumph, augmenting DOX's therapeutic efficacy while mitigating its deleterious side effects.

Areas covered: Recent strides have spotlighted the emergence of DOX conjugates as particularly auspicious avenues for ameliorating DOX-induced cardiotoxicity. These conjugates entail the fusion of DOX through physical or chemical bonds with diminutive natural or synthetic moieties, polymers, biomolecules, and nanoparticles. This spectrum encompasses interventions that impinge upon DOX's cardiotoxic mechanism, modulate cellular uptake and localization, confer antioxidative properties, or refine cellular targeting.

Expert opinion: The endorsement of DOX conjugates as a compelling stratagem to mitigate DOX-induced cardiotoxicity resounds from this exegesis, amplifying safety margins and the therapeutic profile of this venerated chemotherapeutic agent. Within this ambit, DOX conjugates stand as a beacon of promise in the perpetual pursuit of refining chemotherapy-induced cardiac compromise.

Keywords: Anthracyclines; bioconjugation; cardiotoxicity; doxorubicin; free radicals; therapeutic index.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic* / administration & dosage
  • Antibiotics, Antineoplastic* / adverse effects
  • Antibiotics, Antineoplastic* / chemistry
  • Cardiotoxicity* / etiology
  • Cardiotoxicity* / prevention & control
  • Doxorubicin* / administration & dosage
  • Doxorubicin* / adverse effects
  • Drug Carriers* / chemistry
  • Drug Delivery Systems
  • Heart Failure / chemically induced
  • Heart Failure / drug therapy
  • Humans
  • Lipids / chemistry
  • Nanoparticles* / chemistry
  • Polymers / chemistry

Substances

  • Doxorubicin
  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Polymers
  • Lipids