BCN-DOTA (1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid functionalized with a bicyclic nitrogen-rich compound) has emerged as a groundbreaking chelating agent in the field of drug delivery, characterized by its unique structural properties and multifaceted functionality. This compound is a fusion of the well-established DOTA framework, known for its robust metal-chelating abilities, and a bicyclic nitrogen-rich scaffold that enhances its versatility in various therapeutic applications. The synergy between these elements not only improves drug stability and solubility but also enhances targeting precision, making BCN-DOTA a promising candidate for innovative drug delivery systems, particularly in oncology, molecular imaging, and personalized medicine.
Figure 1. Chemistry and three-dimensional structure of DOTA chelators. (Forte E, et al. 2019)
One of the most significant advantages of BCN-DOTA lies in its exceptional stability in physiological environments. This stability is crucial for ensuring that therapeutic agents remain effective until they reach their intended targets. Conventional drug delivery systems often face challenges with premature drug release or degradation, which can lead to diminished efficacy and increased side effects. BCN-DOTA's structural integrity safeguards the drugs it carries, allowing for a more controlled release profile. This is particularly beneficial for hydrophobic drugs that typically struggle to achieve adequate concentrations in systemic circulation. By improving the solubility and bioavailability of these compounds, BCN-DOTA significantly enhances their pharmacokinetics, thereby paving the way for more effective treatment strategies. Additionally, the ability of BCN-DOTA to form stable complexes with various metal ions is a key feature that broadens its applicability in drug delivery systems. This property enables the development of metal-based therapeutic agents that can be employed in targeted therapy and imaging. For instance, the incorporation of radiometals into the BCN-DOTA framework allows for the creation of imaging agents that can visualize tumor sites while simultaneously delivering therapeutic payloads. This dual functionality is particularly advantageous in oncology, where accurate localization of therapeutic agents can dramatically improve treatment outcomes. The possibility of using BCN-DOTA to facilitate both diagnostic and therapeutic functions underscores its potential as a multifunctional tool in modern medicine. Furthermore, BCN-DOTA's capacity to facilitate targeted drug delivery cannot be overstated. By attaching specific ligands or antibodies to the BCN-DOTA structure, researchers can create conjugates that selectively bind to receptors overexpressed on the surface of diseased cells. This targeted approach enhances the therapeutic impact of treatments while minimizing off-target effects that can result in harm to healthy tissues. The precision offered by BCN-DOTA is especially critical in the context of personalized medicine, where therapies are increasingly tailored to the individual needs of patients. This ability to modify the BCN-DOTA structure for different applications highlights its versatility and potential in developing cutting-edge drug delivery systems.
The integration of BCN-DOTA into nanocarrier systems represents another exciting frontier in drug delivery research. When embedded in nanoparticles or liposomes, BCN-DOTA can significantly enhance drug loading capacities and improve controlled release profiles. These nanocarrier systems can encapsulate a wide variety of therapeutic agents, enabling the co-delivery of multiple drugs. Co-delivery strategies are particularly valuable in treating complex diseases such as cancer, where combination therapies often yield better outcomes than single-agent therapies. By leveraging the unique properties of BCN-DOTA alongside advanced nanotechnology, researchers can create optimized delivery systems that maximize therapeutic efficacy and reduce potential side effects. Moreover, BCN-DOTA's unique structural features position it as a candidate for advancing gene therapy applications. The ability to conjugate BCN-DOTA with nucleic acids allows for the precise delivery of therapeutic genes to target cells. This targeted gene delivery is crucial for achieving successful treatment outcomes in genetic disorders. The structural stability of BCN-DOTA ensures that the nucleic acids remain intact during transport, while its capacity for specific targeting enhances cellular uptake and delivery efficiency. This capability aligns with the broader goals of gene therapy, which aims to provide personalized treatments that address the root causes of genetic diseases. BCN-DOTA's potential in diagnostic imaging further complements its therapeutic applications. By coordinating with metal ions that emit signals detectable through imaging techniques, BCN-DOTA can serve as a key component in creating imaging agents that provide real-time insights into biological processes. This dual use of BCN-DOTA not only aids in the visualization of drug distribution but also enhances the overall understanding of treatment dynamics, allowing for better monitoring of therapeutic responses. The combination of drug delivery and imaging capabilities positions BCN-DOTA as a versatile agent that can facilitate both treatment and diagnosis in clinical settings. As the research landscape evolves, the exploration of BCN-DOTA's capabilities continues to expand, with ongoing studies focusing on optimizing drug conjugation techniques, enhancing stability in biological environments, and refining release mechanisms to achieve desired therapeutic effects. Researchers are investigating novel applications of BCN-DOTA in various therapeutic areas, including cardiovascular diseases, infectious diseases, and autoimmune disorders. This ongoing exploration underscores the adaptability and promise of BCN-DOTA as a transformative agent in drug delivery systems.
Alternate Names:
DOTA-BCN
DOTA-BCN-Theranostic
DOTA-1,4-bis(3,4-dihydroxyphenyl)-2,3-butanediol
DOTA-Bis(3,4-dihydroxyphenyl)butanediol
DOTA-BCN conjugate
References:
1. Forte E, et al. Radiolabeled PET/MRI Nanoparticles for Tumor Imaging. J Clin Med. 2019, 9(1):89.
2. Perico ME, et al. The humoral immune response to macrocyclic chelating agent DOTA depends on the carrier molecule. J Nucl Med. 2001, 42(11):1697-703.
The ubiquitous DOTA and its derivatives: the impact of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid on biomedical imaging
Chem Commun (Camb)
Authors: Stasiuk GJ, Long NJ.
Abstract
Over the last twenty-five years 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) has made a significant impact on the field of diagnostic imaging. DOTA is not the only metal chelate in use in medical diagnostics, but it is the only one to significantly impact on all of the major imaging modalities Magnetic Resonance (MR), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Fluorescence imaging. This crossover of modalities has been possible due to the versatility of DOTA firstly, to complex a variety of metal ions and secondly, the ease with which it can be modified for different disease states. This has driven research over the last two decades into the chemistry of DOTA and the modification of the substituent pendant arms of this macrocycle to create functional, targeted and dual-modal imaging agents. The primary use of DOTA has been with the lanthanide series of metals, gadolinium for MRI, europium and terbium for fluorescence and neodymium for near infra-red imaging. There are now many research groups dedicated to the use of lanthanides with DOTA although other chelates such as DTPA and NOTA are being increasingly employed. The ease with which DOTA can be conjugated to peptides has given rise to targeted imaging agents seen in the PET, SPECT and radiotherapy fields. These modalities use a variety of radiometals that complex with DOTA, e.g.(64)Cu and (68)Ga which are used in clinical PET scans, (111)In, and (90)Y for SPECT and radiotherapy. In this article, we will demonstrate the remarkable versatility of DOTA, how it has crossed the imaging modality boundaries and how it has been successfully transferred into the clinic.
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