Engineering imaging probes and molecular machines for nanomedicine

Abstract

Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, life sciences and medicine; it is expected to produce major breakthroughs in medical diagnostics and therapeutics. Due to the size-compatibility of nano-scale structures and devices with proteins and nucleic acids, the design, synthesis and application of nanoprobes, nanocarriers and nanomachines provide unprecedented opportunities for achieving a better control of biological processes, and drastic improvements in disease detection, therapy, and prevention. Recent advances in nanomedicine include the development of functional nanoparticle based molecular imaging probes, nano-structured materials as drug/gene carriers for in vivo delivery, and engineered molecular machines for treating single-gene disorders. This review focuses on the development of molecular imaging probes and engineered nucleases for nanomedicine, including quantum dot bioconjugates, quantum dot-fluorescent protein FRET probes, molecular beacons, magnetic and gold nanoparticle based imaging contrast agents, and the design and validation of zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) for gene targeting. The challenges in translating nanomedicine approaches to clinical applications are discussed. Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, biology, and medicine [1]. It focuses on the development of engineered nano-scale (1100 nm) materials, structures and devices for better diagnostics and highly specific medical intervention in curing disease or repairing damaged tissues. As a basis for nanomedicine, nanotechnology is the science, engineering, and technology related to the understanding and control of matter at the nano-scale, and the development of materials, devices, and systems that have novel properties and functions due to their nano-scale dimensions or components. Nanotechnology also provides new abilities to measure, control and manipulate matter (including soft matter) at the nano-scale what was unthinkable with conventional tools. Owing to the size-compatibility of nano-scale structures with proteins and nucleic acids in living cells, nanomedicine approaches have the potential to provide unprecedented opportunities for achieving a better control of biological processes, and drastic improvements in disease detection, therapy, and prevention, thus revolutionizing medicine. Over the last ten years or so, significant efforts have been made in the US, China, Europe and elsewhere to develop nanomedicine. For example, the US National Institutes of Health has developed a nanomedicine centers network, and invested a significant amount of research funding to nanomedicine development. Just in FY 2009 (Oct. 1, 2008Sept. 30, 2009, the total NIH funding in nanotechnology/ nanoscience projects was more than 410 million US dollars. SPECIAL TOPIC

Applications of nanotechnology in biomedicine

“…Moreover, some nanomaterials are potential florescence probes in relevant technologies. For instance, quantum dots are of high photo stability, high identification accuracy and controllable colors, and have been used as fluorescence imaging probes, fluorescent protein FRET probes and molecular beacons [6]. Atomic force microscopy (AFM) is a powerful tool in the study of biomolecular interactions, and can measure the binding forces at the molecular level of protein/DNA, DNA/ DNA, ligand/receptor and other biomolecule pairs.…”

“…X-ray computed tomography (CT) is widely used in diagnostic medicine. Many kinds of nanomaterials have shown great potentials as CT contrast agents, such as gold, silver, bismuth, and tantalum nanomaterials [6]. Gold nanoparticles have higher atomic number, X-ray absorption coefficient, and longer blood circulation half-life than clinically used CT contrast agents [6].…”

“…Many kinds of nanomaterials have shown great potentials as CT contrast agents, such as gold, silver, bismuth, and tantalum nanomaterials [6]. Gold nanoparticles have higher atomic number, X-ray absorption coefficient, and longer blood circulation half-life than clinically used CT contrast agents [6]. They are also utilized in light scattering imaging, two-photon fluorescence (TPF) imaging and photoacoustic imaging in the cell imaging-based detection for tumors [12].…”

“…They are also utilized in light scattering imaging, two-photon fluorescence (TPF) imaging and photoacoustic imaging in the cell imaging-based detection for tumors [12]. Besides, entrapment with Liposomes can prolong the circulation half-time of traditional contrast agents as iodinated ones [6].…”

“…Compared with gadolinium-based MRI contrast agents, nanoparticle MRI contrast agents circulate longer in the blood, and have higher sensitivity and fewer side-effects [6]. Combining positron emission tomography (PET) with the highresolution, spectroscopic, and contrast enhancement abilities of MRI would make a breakthrough in the detection and monitoring of diseases.…”