Water-soluble polysaccharide-anthracycline conjugates: biological activity

Area of Science:

• Biochemistry
• Materials Science
• Pharmacology

Background:

• Anticancer agents like doxorubicin and daunorubicin face challenges in targeted delivery and toxicity.
• Developing drug delivery systems that enhance efficacy while minimizing side effects is crucial in cancer therapy.

Purpose of the Study:

• To create novel drug-polymer conjugates using doxorubicin/daunorubicin and anionic polysaccharides (hyaluronic acid, carboxy-methylcellulose).
• To evaluate the anticancer properties, cellular uptake, and toxicity of these novel drug-polymer conjugates.

Main Methods:

• Covalent linkage of doxorubicin and daunorubicin to hyaluronic acid and carboxy-methylcellulose.
• Assessment of cell growth and DNA synthesis inhibition.
• Investigation of drug incorporation into cells over time.

Main Results:

• Drug-polymer conjugates exhibited reduced cell toxicity compared to free drugs.
• The molecular weight of the polysaccharide carrier moderately influenced the anthracycline's biological activity.
• Partial drug incorporation into cells was observed, likely via endocytosis and subsequent conjugate cleavage.
• Membrane binding was found to contribute minimally to the overall toxicity.

Conclusions:

• Covalent conjugation of anticancer drugs to anionic polysaccharides offers a promising strategy for improved cancer therapy.
• The developed conjugates allow for precise dose-response determinations and reduced systemic toxicity.
• Endocytosis-mediated cellular uptake and biochemical cleavage are key mechanisms for drug release from these conjugates.