Tumor selective self-assembled nanomicelles of carbohydrate-epothilone B conjugate for targeted chemotherapy

Area of Science:

• Bioconjugation Chemistry
• Nanomedicine
• Cancer Therapeutics

Background:

• Epothilone B (Epo B) shows potent anti-cancer activity but suffers from poor tumor selectivity and narrow therapeutic windows.
• Developing Epo B into effective clinical drugs is hindered by its toxicity and lack of targeted delivery to cancer cells.

Purpose of the Study:

• To design and synthesize self-assembled nanomicelles from an amphiphilic carbohydrate-Epo B conjugate for improved tumor targeting and controlled drug release.
• To evaluate the in vitro and in vivo anticancer efficacy and selectivity of the developed nanomicelles.

Main Methods:

• Synthesis of four Epothilone B-Rhamnose conjugates with disulfide bonds sensitive to glutathione (GSH).
• Self-assembly of conjugate 34 into nanomicelles with surface-displayed Rhamnose for enhanced tumor targeting.
• Assessment of nanomicelle internalization, GSH-triggered Epo B release, and anti-proliferative activity in cancer cells and in vivo models.

Main Results:

• Conjugate 34 formed stable nanomicelles with high Rhamnose surface density, facilitating tumor cell uptake.
• Internalized nanomicelles released active Epothilone B upon cleavage of the disulfide bond in the presence of elevated intracellular GSH levels.
• The nanomicelle formulation demonstrated significant in vitro and in vivo anticancer efficiency and improved selectivity compared to free Epo B.

Conclusions:

• Self-assembled nanomicelles based on carbohydrate-Epo B conjugates offer a promising strategy for targeted cancer therapy.
• The GSH-sensitive disulfide linkage enables controlled release of active Epo B within tumor cells, enhancing therapeutic outcomes.
• This approach addresses the limitations of Epo B, paving the way for its potential clinical application in oncology.