6-Aminocaproic Acid: Medical Applications and Spectrofluorimetric Determination

General Description

6-Aminocaproic acid plays a crucial role in enhancing cancer diagnostic and therapeutic techniques by improving the stability and efficacy of indocyanine green (ICG) in the development of the mPEG-ACA-ICG conjugate. This conjugate, facilitated by 6-aminocaproic acid, offers enhanced bioenvironmental stability, photothermal efficiency, and tumor-targeting capabilities for effective cancer treatment. Additionally, 6-aminocaproic acid is utilized in the spectrofluorimetric determination method for precise measurement of its concentrations in biological samples, demonstrating high sensitivity and accuracy. Overall, 6-aminocaproic acid proves to be a pivotal component in advancing non-invasive cancer treatments and diagnostics while providing a reliable analytical tool for the quantitative analysis of this essential medical compound.

Figure 1. 6-Aminocaproic acid

Medical Applications

6-Aminocaproic acid plays a critical role in advancing medical applications, particularly in enhancing cancer diagnostic and therapeutic techniques. This compound serves as a hydrophobic linker in the development of a novel conjugate aimed at improving the properties and functionalities of indocyanine green (ICG), a dye used in medical imaging and therapy. By integrating 6-aminocaproic acid with ICG and polyethylene glycol (PEG), researchers have significantly improved the bioenvironmental stability, photothermal efficiency, and body retention time of the dye, crucial for effective cancer treatment. The innovative conjugate, known as mPEG-ACA-ICG, utilizes 6-aminocaproic acid to bridge ICG with PEG, resulting in a stable, amphiphilic compound that can self-assemble into micellar aggregates in aqueous solutions. This structure dramatically enhances the stability of the conjugate, addressing one of the primary limitations of free ICG—its propensity to degrade and aggregate in biological environments. The addition of 6-aminocaproic acid ensures that the conjugate has a lower critical micelle concentration (CMC) than its predecessors without the 6-Aminocaproic acid linker, indicating better solubility and stability in biological fluids. Moreover, the inclusion of 6-aminocaproic acid into the ICG molecule enhances its photothermal conversion efficiency, which is crucial for photothermal cancer therapy (PTT). This means that upon exposure to near-infrared light, the mPEG-ACA-ICG conjugate is more efficient in converting light into heat, effectively targeting and destroying tumor cells with minimal damage to surrounding healthy tissues. In clinical settings, the mPEG-ACA-ICG conjugate facilitated by 6-aminocaproic acid has shown promising results in fluorescence image-guided surgery (FIGS) and photothermal therapy. In vivo experiments demonstrated that mPEG-ACA-ICG nanomicelles could achieve a maximum tumor inhibition rate of 72.6%, underscoring the potential of 6-aminocaproic acid in enhancing the efficacy of cancer treatments. Overall, 6-aminocaproic acid is a pivotal component in the mPEG-ACA-ICG conjugate, offering significant improvements in the stability, efficacy, and safety of indocyanine green-based theranostics. This highlights the potential of 6-aminocaproic acid in advancing non-invasive cancer treatments and diagnostics, paving the way for more effective and targeted therapeutic strategies. ¹

Spectrofluorimetric Determination

The spectrofluorimetric determination of 6-Aminocaproic acid, a vital antihemorrhagic and antifibrinolytic agent, utilizes a sensitive and cost-effective method facilitated by the benzofurazan-based fluorophore, specifically 4-chloro-7-nitrobenzofurazan (NBD-Cl). This novel analytical technique offers precise measurement of 6-Aminocaproic acid concentrations in biological samples, including human plasma and urine, making it highly relevant for medical and research purposes. In the determination process, 6-Aminocaproic acid reacts via nucleophilic substitution with the primary amine group on NBD-Cl in a borate buffer solution at pH 9. This reaction yields a fluorescent yellow product. The fluorescence of this product is then measured spectrofluorimetrically at an emission wavelength of 525 nm after excitation at 472 nm. The precision of this method is highlighted by its ability to detect 6-Aminocaproic acid at concentrations as low as 0.033 μg/mL, with a quantitation limit of 0.101 μg/mL, and a linear range of 0.1 to 0.7 μg/mL. Optimization studies were conducted to refine the variables affecting the method’s efficiency, ensuring the accurate determination of 6-Aminocaproic acid. This meticulous optimization allows for the method’s reliable use in clinical and laboratory settings, where accurate dosing and monitoring of 6-Aminocaproic acid are critical. The spectrofluorimetric determination method has been effectively applied to laboratory-prepared samples of 6-Aminocaproic acid, achieving an average recovery rate of 100.19 ± 0.72%. This indicates a high level of accuracy and precision, without interference from common excipients found in dosage forms. Furthermore, the method’s utility was extended to analyze 6-Aminocaproic acid levels in spiked human plasma and urine samples, demonstrating its applicability in a real-world clinical context. Overall, the development of this spectrofluorimetric method represents a significant advancement in the analytical chemistry of 6-Aminocaproic acid, offering a robust, efficient, and highly sensitive tool for the quantitative analysis of this crucial medical compound in various biological matrices. ²

Reference

1. Hu Q, Wang K, Qiu L. 6-Aminocaproic acid as a linker to improve near-infrared fluorescence imaging and photothermal cancer therapy of PEGylated indocyanine green. Colloids Surf B Biointerfaces. 2021; 197: 111372.

2. Anwer EF, Nour El-Deen DAM, Derayea SM, Omar MA. Benzofurazan -based fluorophore for the spectrofluorimetric determination of 6-Aminocaproic acid: Application to spiked human plasma and urine. Spectrochim Acta A Mol Biomol Spectrosc. 2022; 268: 120723.