June 24th, 2015

Various diagnostic imaging techniques are currently used for clinical imaging/disease diagnosis. The accuracy of diagnosis is mainly based on the type of energy used (such as X-ray, sound waves, photons and positrons) to derive the visual information, as well as the degree of spatial resolution (mesoscopic or microscopic) and the level of information that can be obtained (physiological, anatomical or molecular). Based on potential health hazards imposed by type of energy used, clinical imaging modalities can be broadly categorized as ionizing and non-ionizing modalities. Compared to ionizing imaging techniques (for example X-ray imaging), non-ionizing imaging techniques make use of harmless low-energy input radiations (such as visible light and near infra-red light) that are safer to image the targeted subjects. Furthermore, such non-ionizing techniques allow repeated imaging procedures with increased dosage levels for image clarification and verification. Extensive research is going on worldwide to enhance image resolution and therefore to further popularize non-ionizing imaging techniques in clinical imaging and diagnosis.

Owing to recent spectacular advances in nanochemistry and nanomaterials sciences, substantial progress in the design and synthesis of synthetic nanoscale hybrid materials has been achieved with new or improved properties. This allows scientists to fabricate new hybrid materials that can be used in individual and multimodal imaging techniques simultaneously. A review published in Science Bulletin by Prof. Yanli Zhao coauthored with Dr. Sivaramapanicker Sreejith, Tran Thi Mai Huong, and Dr. Parijat Borah showcased various strategies for the design of organic-inorganic nanohybrids toward fluorescent, Raman, photoacoustic and combined multimodality imaging. The team stated that "design of multifunctional nanohybrids offers great opportunities to integrate additional functionalities, thus opening up new imaging and therapeutic avenues".
Optical imaging modalities such as fluorescence, photoacoustic and Raman bioimaging were mainly highlighted in this review by giving emphasis on the use of various hybrid materials as single and multimodal image contrast materials. Fluorescence imaging is widely adopted as the mainstay of microscopy in service of biology due to its high selectivity of targets. An ideal fluorescence imaging probe will be the one with robust photostability, excellent fluorescence and no toxicity in biological systems. However, the existing organic dyes, fluorescent proteins and quantum dots are either unstable or toxic to biological systems. Hence, the development of novel organic-inorganic nanohybrids is required, which combine strong fluorescence, high photostability and great biocompatibility in one single entity. In the review, authors stated that hybrid materials prepared from silica are promising examples for fluorescence imaging. Similarly, photosensitizer loaded mesoporous silica nanoparticles (MSNPs) and dye loaded MSNPs wrapped with an ultrathin layer of graphene oxide (GO) also show excellent performance for fluorescence imaging.
It was stated in the review that a potential approach to obtain precise high resolution images may be by the use of multimodal imaging techniques for example a combination of fluorescence and Raman imaging. Raman imaging technique relied on Raman scattering or inelastic scattering of light has been used to characterize various sp2 carbon-containing nanomaterials such as carbon nanotubes and graphene. It has attracted a lot of interest as an excellent noninvasive bioimaging tool because of its many desirable properties such as minimal photobleaching and high resolution. However, Raman scattering is very weak and demands advanced techniques such as surface-enhanced Raman scattering (SERS) to magnify the signal intensity. It was highlighted that a combination of GO with gold nanoparticles (AuNPs) could show bimodal fluorescence and Raman imaging.
Similarly, they also reviewed recently emerging techniques such as photoacoustic imaging (PAI) that has been widely used to provide high spatial resolution images. The advantages of this technique are offset by the fact that tissues often experience low optical absorption due to tissue scattering and negative influence of some endogenous agents like hemoglobin. Nanoparticle-based contrast agents were then developed to enhance the photoacoustic signals for tissue imaging. The team reported a method to prepare a GO-based nanosandwich hybrid. The GO was encapsulated by mesoporous silica on its both sides, followed by loading of a two-photon active dye and then sealed with poly(acrylic acid) to obtain the nanosandwich hybrid. The hybrid has low cytotoxicity and high ability to afford excellent photoacoustic and fluorescent bimodal imaging in cancer cells and tissue mimics.
The recent fabrication of novel hybrid nanomaterials has been proven useful for applications in fluorescent, Raman, photoacoustic and combined bioimaging. Although there are still some challenges to be addressed, including the long-term toxicity of nanohybrids and the difficulty for translating the developed nanohybrids to clinical bioimaging uses, state-of-the-art advancements of organic-inorganic hybrids have already shown their significant application potentials for clinical bioimaging especially in screening cancerous cells.