Responsive Prodrug Self-Assembled Vesicles for Targeted Chemotherapy in Combination with Intracellular Imaging

Area of Science:

• Nanomedicine
• Bioconjugate Chemistry
• Cancer Therapeutics

Background:

• Controlled drug delivery systems with fluorescence reporters are crucial in nanomedicine.
• Developing prodrugs for direct assembly into such systems remains a challenge.
• Amphiphilic prodrugs offer potential for self-assembly into functional nanostructures.

Purpose of the Study:

• To design and synthesize an amphiphilic chlorambucil-based prodrug.
• To investigate the self-assembly of the prodrug into nanovesicles for targeted cancer therapy.
• To evaluate the drug release, cellular uptake, and therapeutic efficacy of the nanovesicles.

Main Methods:

• Synthesis of a chlorambucil prodrug incorporating a fluorescence reporter and d-mannose ligand.
• Characterization of nanovesicle self-assembly and drug loading.
• In vitro studies using MCF-7 cancer cells overexpressing d-mannose receptors.
• Assessment of cellular internalization, drug release kinetics, and fluorescence imaging.
• Evaluation of therapeutic efficacy compared to free chlorambucil.

Main Results:

• The amphiphilic prodrug successfully self-assembled into glutathione-responsive nanovesicles.
• Nanovesicles demonstrated selective internalization by d-mannose receptor-overexpressing cancer cells.
• Internalization triggered nanovesicle dissociation and chlorambucil release, accompanied by red-shifted fluorescence.
• The nanovesicles exhibited enhanced selectivity and superior therapeutic efficiency compared to free chlorambucil.

Conclusions:

• A novel chlorambucil-based prodrug can self-assemble into targeted, fluorescence-reporting nanovesicles.
• These nanovesicles enable selective cancer therapy and intracellular imaging via d-mannose receptor targeting.
• The developed system shows promise for improved cancer treatment strategies in nanomedicine.