Theranostic nanomaterials for image-guided gene therapy
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troduction The term “theranostics,” a portmanteau word of therapeutics and diagnostics, is a proposed methodology for increasing treatment efficacy and safety and for monitoring the response to treatment at the same time. The integration of therapeutic and diagnostic functions within a single dose allows the development of effective curing protocols by simultaneously monitoring the results of a new medication test (Figure 1). In the last few years, an increasing number of articles on theranostics have reported imaging agents that can predict or monitor therapy. This image-guided therapy allows for the tailoring of optimized treatment for individual patients and would be of great interest to the field of personalized medicine. Theranostics relies on emerging advances in nanotechnology, wherein the detection of nanomaterials could occur before, during, or after the treatment regimen.1 Molecular imaging permits non-invasive monitoring of the distribution of theranostic nanocarriers. It can also provide very rapid feedback on specific targeting and delivery of therapeutic agents using real-time monitoring. Nanoparticles have specific advantages for theranostics that are not found for small molecules. They possibly have a longer circulation half-life, and they are useful for applications such as cardiac blood pool imaging, tumor contrast, diagnosis of inflammation, and sustained systemic drug delivery.2
Gene therapy refers to an approach by which abnormal genes within an individual’s cells are supplemented or altered with normal ones to modulate the disease manifestation. Generally, two types of therapeutic strategies have been used in gene therapy: gain-of-function and loss-of-function.3 For gain-of-function, complementary DNA (cDNA) or messenger RNA (mRNA) needs to be delivered to increase expression of a target protein, which is mostly done by viral vectors (viruses for gene delivery, such as retrovirus, adenovirus, lentivirus, etc.).4 In contrast, for loss-of-function, the function or synthesis of a target protein can be blocked when an antisense oligonucleotide (AS-ODN), a small interfering RNA (siRNA) or an aptamer, is delivered by non-viral vectors (for more information on AS-ODN, siRNA, and aptamer, see References 5 and 6). Since the first conceptualization of gene therapy in 1972, a number of clinical trials have been conducted using various techniques.7 Clinical approval of Gendicine by the Chinese State Food and Drug Administration was the world’s first commercial gene therapy. Gendicine is a recombinant adenovirus engineered to express wild-type-p53, a tumor suppressor protein, for the treatment of cancer with mutated p53.8 The landmark clinical trials included the delivery of RPE65 (retinal pigment epithelium-specific 65 kDa protein) cDNA using
Seung Rim Hwang, College of Pharmacy, Chosun University, South Korea; [email protected] Sook Hee Ku, Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, South Korea; [email protected] Min Kyung Joo, Center for Theragnosis, B
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