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A binding ligand such as an antibody that can specifically bind to receptors expressed at a disease site is an essential component of such constructs. Different chemical methods have been widely used to apply antibodies for delivery systems; however, they typically result in impairment or loss of antibody functionality. En- zyme-mediated conjugation approaches have been developed to over- come this major disadvantage of conventional chemical methods. Sortase, an enzyme derived from Staphylococcus aureus, is able to provide a biochemically robust, highly reproducible, and site-specific coupling method for the conjugation of antibodies to pharmaceutical agents, nanoparticles, and cells for drug delivery, molecular imaging, and cell homing. Here, we review the use of sortase and other enzyme- based methods as bioconjugation tools with a focus on cardiovascular applications. (Trends Cardiovasc Med 2012;22:105-111) © 2012 Elsevier Inc. All rights reserved. • Introduction Antibody tagging is one of the essential methods to achieve targeted molecular imaging and targeted drug or regenera- tive cell delivery for the diagnosis and treatment of diseases. Targeted drug de- livery can improve treatment efficacy of a variety of conditions, such as cancer, diabetes, and cardiovascular and inflam- matory diseases. Although the treatment and imaging of cancerous tumors is the most widely studied application of tar- geted delivery, this approach has gained increasing interest in other areas such as cardiovascular diseases. Cardiovascular disease (CVD) is a major health issue and the leading cause of mortality and morbidity worldwide (Roger et al. 2011). Therefore, there is an urgent need to develop better diagnostic imaging agents for vulnerable plaque detection, for example, as well as more efficient treatment options such as stem cell de- livery for cardiac repair. The key to achieving these objectives lies in more effective use of medication that can be targeted directly to the diseased tissue. Targeting drugs to desired areas not only enhances the potency of the drugs but also minimizes side effects because the injected dose is greatly reduced. Conventionally, targeted delivery is achieved via chemical conjugation of Hang T. Ta and Christoph E. Hagemeyer are at the Vascular Biotechnology Labora- tory, Baker IDI Heart and Diabetes Insti- tute, Melbourne, VIC 3004, Australia. Hang T. Ta and Karlheinz Peter are at the Athero- thrombosis and Vascular Biology Laboratory, Baker IDI Heart and Diabetes Institute, Mel- bourne, VIC 3004, Australia. *Address correspondence to: Christoph E. Hagemeyer, PhD, Vascular Biotechnology Laboratory, Baker IDI Heart and Diabetes Institute, Street: 75 Commercial Road, Mel- bourne, VIC 3004, Australia. Tel.: (+61) 3 8532 1494; fax: (+61) 3 8532 1100; e-mail: christoph.hagemeyer@bakeridi.edu.au. Published online 11 August, 2012. © 2012 Elsevier Inc. All rights reserved. 1050-1738/$-see front matter TCM Vol. 22, No. 4, 2012 105