Overcoming multidrug resistance through fucoidan from molecular mechanisms to nanomedicine applications

Area of Science:

• Biochemistry
• Pharmacology
• Nanomedicine

Background:

• Multidrug resistance (MDR) is a significant challenge in cancer chemotherapy, driven by factors like P-glycoprotein (P-gp) efflux pumps.
• Fucoidan, a sulfated polysaccharide from brown seaweeds, exhibits anti-MDR properties by targeting key resistance mechanisms.

Purpose of the Study:

• To review the mechanisms by which fucoidan overcomes MDR and enhances chemosensitivity.
• To explore the role of fucoidan structure-function relationships in its biological activity.
• To highlight the potential of fucoidan-based nanomedicine for cancer therapy.

Main Methods:

• Literature review integrating mechanistic evidence on fucoidan's effects on apoptosis, P-gp activity, and signaling pathways (PI3K/Akt, NF-κB).
• Analysis of structure-function determinants influencing fucoidan's efficacy.
• Overview of fucoidan-based nanocarrier design and applications.

Main Results:

• Fucoidan downregulates P-gp expression and inhibits its ATPase activity, reducing drug efflux.
• Fucoidan modulates signaling pathways, induces apoptosis, and regulates oxidative stress and inflammation.
• Fucoidan-based nanocarriers can co-deliver drugs, target tumors, and respond to tumor microenvironment stimuli.

Conclusions:

• Fucoidan acts as an effective apoptosis-oriented adjuvant to overcome MDR and restore chemosensitivity.
• Fucoidan-enabled nanomedicine offers a promising strategy for enhancing cancer therapy.
• Standardization and clinical evaluation are crucial for the translation of fucoidan-based therapies.