H₂O₂-Responsive Theranostic Prodrugs for Cancer-Selective DNA Alkylation and Real-Time Fluorescence Imaging in Living Cells

Letters & Science (College of) / Chemistry & Biochemistry

Project Description

Objectives:
• Design and synthesize hydrogen peroxide (H₂O₂)-responsive prodrugs that selectively release DNA-alkylating agents in cancer cells.
• Incorporate fluorescent reporters into prodrugs to allow real-time monitoring of activation in living cells.
• Evaluate the selectivity and efficacy of synthesized prodrugs in cancer versus normal cell lines.
Methodology:
• Organic Synthesis: The student will perform multi-step synthesis of H₂O₂-activatable prodrugs with fluorescent tags. This includes reaction optimization, purification, and characterization (NMR, LC–MS).
• Chemical Analysis: Characterize intermediates and final compounds to confirm structure and purity.
• In Vitro Evaluation (Collaborative): Prepared prodrugs will be tested in cultured cells for selective activation and cytotoxicity, tracked by fluorescence imaging and viability assays.
• Data Analysis: Quantitative analysis of reaction yields, purity, and fluorescence activation will inform iterative improvements in prodrug design.

Tasks and Responsibilites

• Execute multi-step organic syntheses of H₂O₂-responsive prodrugs.
• Purify compounds using chromatography and characterize them using NMR, LC–MS, and fluorescence spectroscopy.
• Maintain accurate lab notebooks and document experimental procedures and observations.
• Collaborate with team members performing cell-based assays to provide compounds for biological testing.
• Analyze data from chemical synthesis and contribute to discussions on improving reaction efficiency and prodrug design.
• Present progress in lab meetings and prepare a final summer report.

Desired Qualifications

None listed.