Project Description
This research aims to develop and investigate small-molecule theranostics that selectively activate in response to elevated hydrogen peroxide (H₂O₂) levels—a hallmark of triple-negative breast cancer (TNBC) cells. The dual-function molecules will enable both cancer-selective cytotoxicity and real-time fluorescence-based monitoring of drug activation and localization in live cells. The project will contribute to the development of targeted therapies with reduced systemic toxicity and built-in bioimaging capabilities.
Methodology: Building on a recently published study, the student will focus on the synthesis, characterization, and biological evaluation of H₂O₂-responsive theranostic agents:
1. Chemical Synthesis and Characterization:
a) Synthesize boronate-masked nitrogen mustard prodrugs conjugated to profluorophores;
b) Characterize the compounds using NMR, mass spectrometry, and HPLC.
2. H₂O₂-Triggered Activation Studies:
a) Assess H₂O₂-induced oxidative deboronation and release of the active drug and fluorophore;
b) Quantify fluorescence turn-on response upon H₂O₂ treatment in vitro.
3. Biological Evaluation in Cell Models:
a) Culture TNBC cells (e.g., MDA-MB-468) and normal epithelial cells (e.g., MCF-10A);
b) Evaluate cytotoxicity using MTT or CellTiter-Glo assays;
c) Perform fluorescence microscopy to track drug activation and localization in mitochondria and nucleus of living cells.
Tasks and Responsibilites
The undergraduate student will primarily focus on the synthesis and characterization of hydrogen peroxide–responsive theranostic agents. Under close supervision, their responsibilities will include:
Literature Familiarization: Read and discuss key background literature related to ROS-responsive prodrugs and boronate chemistry. Review safety data sheets (SDS) and standard operating procedures relevant to planned experiments.
Chemical Synthesis: Assist in planning and carrying out multi-step organic syntheses of boronate-masked nitrogen mustards and profluorophore conjugates. Follow established protocols for reaction setup, monitoring, and work-up using standard laboratory techniques (e.g., extraction, filtration, evaporation).
Purification and Characterization: Purify synthesized compounds using column chromatography and recrystallization. Characterize products using thin-layer chromatography (TLC), NMR spectroscopy, and mass spectrometry under guidance.
Laboratory Maintenance and Preparation: Prepare reagents, stock solutions, and glassware for reactions. Maintain a clean and organized workspace and adhere to chemical safety protocols.
Data Recording and Communication: Keep a detailed laboratory notebook with procedures, observations, and yields. Participate in weekly group meetings to discuss progress and troubleshoot experiments.
Through this experience, the student will develop foundational skills in synthetic organic chemistry, chemical handling, purification methods, and scientific documentation. This training will serve as a strong stepping stone for future research opportunities or graduate study in chemistry or biomedical sciences.
Desired Qualifications
None Listed.