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Quantitative molecular profiling of biomarkers for pancreatic cancer with functionalized quantum dots.

ABSTRACT: Applications in nanomedicine, such as diagnostics and targeted therapeutics, rely on the detection and targeting of membrane biomarkers. In this article we demonstrate absolute quantitative profiling, spatial mapping, and multiplexing of cancer biomarkers using functionalized quantum dots (QDs). We demonstrate highly selective targeting molecular markers for pancreatic cancer with extremely low levels of nonspecific binding. We confirm that we have saturated all biomarkers on the cell surface, and, in conjunction with control experiments, extract absolute quantitative values for the biomarker density in terms of the number of molecules per square micron on the cell surface. We show that we can obtain quantitative spatial information of biomarker distribution on a single cell, important because tumors' cell populations are inherently heterogeneous. We validate our quantitative measurements (number of molecules per square micron) using flow cytometry and demonstrate multiplexed quantitative profiling using color-coded QDs.This paper demonstrates a nice example for quantum dot-based molecular targeting of pancreatic cancer cells for advanced high sensitivity diagnostics and potential future selective therapeutic purposes.

SUBMITTER: Lee KH

PROVIDER: S-EPMC3354032 | biostudies-other | 2012 Oct

REPOSITORIES: biostudies-other

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Quantitative molecular profiling of biomarkers for pancreatic cancer with functionalized quantum dots.

Lee Kwan Hyi KH Galloway Justin F JF Park Jeaho J Dvoracek Charlene M CM Dallas Matthew M Konstantopoulos Konstaninos K Maitra Anirban A Searson Peter C PC

Nanomedicine : nanotechnology, biology, and medicine 20120201 7

Applications in nanomedicine, such as diagnostics and targeted therapeutics, rely on the detection and targeting of membrane biomarkers. In this article we demonstrate absolute quantitative profiling, spatial mapping, and multiplexing of cancer biomarkers using functionalized quantum dots (QDs). We demonstrate highly selective targeting molecular markers for pancreatic cancer with extremely low levels of nonspecific binding. We confirm that we have saturated all biomarkers on the cell surface, a ...[more]

PMID: 22306154

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Project description:Nanotechnology is a growing industry with wide ranging applications in consumer product and technology development. In the biomedical field, nanoparticles are finding increasing use as imaging agents for biomolecular labeling and tumor targeting. The nanoparticle physiochemical properties must be tailored for the specific application. For example, nanoparticle chemical and physical stability in the biological milieu (no oxidation, aggregation, agglomeration or toxicity) are often required. Nanoparticles used for biomolecular fluorescent imaging should also have high quantum yield (QY). The aim of this paper is to examine the QY, stability, and cell toxicity of a series of positive, negative and neutral surface charge quantum dot (QD) nanoparticles. Simple protocols are described to prepare water soluble QDs by modifying the surface with thiol containing antioxidant ligands and polymers keeping the QD core/shell composition constant. The ligands used to produce negatively charged QDs include glutathione (GSH), N-acetyl-L-cysteine (NAC), dihydrolipoic acid (DHLA), tiopronin (TP), bucilliamine (BUC), and mercaptosuccinic acid (MSA). Ligands used to produce positively charged QDs include cysteamine (CYS) and polyethylenimine (PEI). Dithiothreitol (DTT) was used to produce neutral charged QDs. Commercially available nonaqueous octadecylamine (ODA) capped QDs served as the starting material. Our results suggest that QD uptake and cytotoxicity are both dependent on surface ligand coating composition. The negative charged GSH coated QDs show superior performance exhibiting low cytotoxicity, high stability, high QY and therefore are best suited for bioimaging applications. PEI coated QD also show superior performance exhibiting high QY and stability. However, they are considerably more cytotoxic due to their high positive charge which is an advantageous property that can be exploited for gene transfection and/or tumor targeting applications. The synthetic procedures described are straightforward and can be easily adapted in most laboratory settings.

Project description:Singlet fission is an exciton multiplication process in organic molecules in which a photogenerated spin-singlet exciton is rapidly and efficiently converted to two spin-triplet excitons. This process offers a mechanism to break the Shockley-Queisser limit by overcoming the thermalization losses inherent to all single-junction photovoltaics. One of the most promising methods to harness the singlet fission process is via the efficient extraction of the dark triplet excitons into quantum dots (QDs) where they can recombine radiatively, thereby converting high-energy photons to pairs of low-energy photons, which can then be captured in traditional inorganic PVs such as Si. Such a singlet fission photon multiplication (SF-PM) process could increase the efficiency of the best Si cells from 26.7% to 32.5%, breaking the Shockley-Queisser limit. However, there has been no demonstration of such a singlet fission photon multiplication (SF-PM) process in a bulk system to date. Here, we demonstrate a solution-based bulk SF-PM system based on the singlet fission material TIPS-Tc combined with PbS QDs. Using a range of steady-state and time-resolved measurements combined with analytical modeling we study the dynamics and mechanism of the triplet harvesting process. We show that the system absorbs >95% of incident photons within the singlet fission material to form singlet excitons, which then undergo efficient singlet fission in the solution phase (135 ± 5%) before quantitative harvesting of the triplet excitons (95 ± 5%) via a low concentration of QD acceptors, followed by the emission of IR photons. We find that in order to achieve efficient triplet harvesting it is critical to engineer the surface of the QD with a triplet transfer ligand and that bimolecular decay of triplets is potentially a major loss pathway which can be controlled via tuning the concentration of QD acceptors. We demonstrate that the photon multiplication efficiency is maintained up to solar fluence. Our results establish the solution-based SF-PM system as a simple and highly tunable platform to understand the dynamics of a triplet energy transfer process between organic semiconductors and QDs, one that can provide clear design rules for new materials.

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Quantitative molecular profiling of biomarkers for pancreatic cancer with functionalized quantum dots.

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Quantitative molecular profiling of biomarkers for pancreatic cancer with functionalized quantum dots.

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