Despite the fact that UCNs have been used in diverse biological applications, their developments in the various fields are still largely in the early stages. Further research is required to overcome existing limitations and issues so as to unleash the particles' full potential in the various applications. In terms of bioimaging, targeted tumor labeling in cell cultures and animal models has been attained. However, to date, many of these imaging studies have focused mainly on achieving suitably modified particles and characterizing their internalization, selectivity and biodistribution. For UCNs to be successful in vivo diagnostic agents, the existing biocompatibility concerns must be addressed. Any small adjustments to the particles' properties such as size, composition and coating will result in different behaviors in the biological systems such as different cytotoxicity levels, biodistributions and excretion routes. Hence, systematic studies to examine the relationship of the particles' properties and their biological behavior have to be carried out. Furthermore, UCNs possess great potential in disease understanding. This is particularly the case for cancer and infectious diseases in which the biodistribution of the pathogens or diseased cells have great repercussion to the disease progression and treatment efficacies. Here, UCNs can be used as a tool for long term tracking of these distributions and possibly solving more mysteries of the disease manifestations.
For detection and sensing, the submicron UC particles have limited the strategies to the device formats of LFT and microarrays. This is because LRET is often utilized when performing the homogeneous assay in solution. Hence, the particles' size becomes an issue as LRET is largely distance-dependent and the efficiency falls off drastically as the distance between the donor (i.e., particles) and the acceptor increases. With the successful synthesis of smaller UCNs, the development and performance of homogeneous UCN-based assays are expected to pick up quickly in the future, propelling these assays as the emerging alternative. In terms of target recognition, future UCN-based assays are expected to evolve accordingly to the discovering of new and better target recognition partners and will not be limited to just antibody-antigen interactions or DNA hybridizations. For example, carbohydrate-protein or aptamer-protein interactions may be used instead. Therefore, it is highly expected that UCNs will play an essential role in the development of the next generation of POC diagnostics.
UCNs have also shown their potential as therapeutic agents, acting as nanotransducers for PDT and delivery vehicles for drugs and genes. To develop UCN-based PDT as a clinical cancer treatment, systematic evaluations of PDT efficacy, especially parameters such as photosensitizer-UCNs ratio, tumor-targeting specificity and optimal light dose, should be performed. Additionally, in vivo penetration depth studies are required to provide a more realistic assessment concerning the feasibility of UCN-based PDT in treating deep tumors. Furthermore, this PDT strategy can be developed as an alternative treatment option for nononcological diseases, such as infectious diseases as ROS are also expected to have effects on pathogens. Conversely, UCNs as drug or gene carriers is still very much in its infancy. The next major development in this field should utilize the particles' inherent unique optical properties to establish them as nanocarriers with both tracking and on-command release capabilities.
Financial & competing interests disclosure
The authors would like to acknowledge the financial support from A*STAR SBIC and the National University of Singapore. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Nanomedicine. 2011;6(7):1273-1288. © 2011 Future Medicine Ltd.
Cite this: Applications of Upconversion Nanoparticles in Imaging, Detection and Therapy - Medscape - Sep 01, 2011.