Development of Quantum Dot Probes for Near-Infrared Fluorescence Imaging of Breast Cancer Angiogenesis

摘要

The overall objective of this proposal is to develop cyclic RGD peptide conjugated biocompatible quantum dot nanoparticles for near-infrared fluorescence imaging of breast cancer angiogenesis. The two hypotheses to be tested are that: 1) the integrin alpha(v)beta(3) antagonist, when conjugated with semiconductor nanocrystals, will not change the fluorescent properties of the QDs significantly; and 2) the QD-based breast cancer angiogenesis probes are specific enough to recognize the integrin receptor and bright enough for effective detection in preclinical animal models. Specific Aim 1: to prepare water-soluble QD-RGD conjugates and characterize the probes in vitro. Specific Aim 2: to assess the tumor targeting efficacy of QD-RGD in breast cancer model. Major Findings: Although biocompatible quantum dots in theory is superior to organic dyes for long-term, multi-target and highly sensitive imaging, however, the current surface coating techniques do not offer enough stability of QDs in biological medium. On the other hand, NIR fluorescent dyes labeled RGD peptides demonstrated highly sensitive and semi-quantitative NIR fluorescence images for tumor detection in preclinical xenograft models. This non-invasive optical imaging approach provides the opportunity for rapid and cost-effective studies before more costly radionuclide-based imaging studies.