Stabilized multifunctional luminescent nanoparticles for cancer targeting and imaging.
- Have improved stable and tunable optical properties to allow for sensitive detection and multicolor imaging.
- Are nontoxic both in vitro and in vivo.
Prostate cancer is the leading cause of cancer incidence in men with 200,000 new cases each year and the second leading cause of cancer death in men in the United States. As the need for personalized cancer treatments increase, nanoparticle delivery of chemotherapy drugs and/or gene therapy agents has become a major focus due to direct targeting of nanoparticles to affected tissue. In addition, nanoparticles delivered specifically to tumor tissue can provide a useful tool for tumor imaging. There are, however, several complications in using nanoparticles in vivo. For example, the optical properties of quantum dots (QDs), a commonly used fluorescent tag, change dramatically when pH and salt conditions change. Specifically, shifts in the absorption and emission spectra and loss of fluorescence intensity can occur and decrease the sensitivity for QD detection in the body. In addition, QD nanoparticles can be metabolized too quickly and can also be toxic.
Nanoparticles are of much interest as both an in vivo imaging tool and a drug delivery device; however, they can be extremely unstable in vivo causing complications in detection and bioavailability. In order to stabilize the optical and physiological properties of QD nanoparticles, researchers at Emory have developed triblock copolymer coated QD nanoparticles. The nanoparticle consists of a CdSe-ZnS quantum dot protected by a tri- nÃ‚-octylphosphine oxide (TOPO) coordinating ligand and an amphiphilic polymer coating. The triblock copolymer consists of a polybutylacrylate segment, a polyethylacrylate segment, a polymethacrylic acid segment, and a hydrophobic hydrocarbon side chain modified with an 8-carbon side chain. The side chain strongly interacts with the hydrophobic tails of TOPO which allows for self-assembly of the QD coating. Block copolymer coated QD nanoparticles are protected from alterations in absorption and emission spectra as well as fluorescence intensity due to changes in pH or salt conditions, allowing for sensitive and consistent multicolor imaging. In addition, these nanoparticles have increased resistance to hydrolysis and enzymatic degradation making them better suited for in vivo applications compared to uncoated QD nanoparticles. Copolymer coated nanoparticles are efficiently targeted to affected cells and tissues in vitro and in vivo which allows for specific and sensitive imaging and delivery of cargo. This copolymer coated QDs could be used for a variety of applications including diagnostics, therapeutics, drug delivery, and as a research tool.
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QD nanoparticles were successfully targeted to human prostate tumor xenografts in a mouse model, had improved fluorescence, reduced particle aggregation, and increased protection against physiological degradation.
Publication: Gao X et al. Nat Biotechnol (2004). 22(8):969-76.