Pharmacokinetics of Chlorin e6-Cobalt Bis(Dicarbollide) Conjugate in Balb/c Mice with Engrafted Carcinoma

Abstract

The necessary precondition for efficient boron neutron capture therapy (BNCT) is control over the content of isotope 10B in the tumor and normal tissues. In the case of boron-containing porphyrins, the fluorescent part of molecule can be used for quantitative assessment of the boron content. Study Objective: We performed a study of the biodistribution of the chlorin e6-Cobalt bis(dicarbollide) conjugate in carcinoma-bearing Balb/c mice using ex vivo fluorescence imaging, and developed a mathematical model describing boron accumulation and release based on the obtained experimental data. Materials and Methods: The study was performed on Balb/c tumor-bearing mice (CT-26 tumor model). A solution of the chlorin e6-Cobalt bis(dicarbollide) conjugate (CCDC) was injected into the blood at a dose of 10 mg/kg of the animal’s weight. Analysis of the fluorescence signal intensity was performed at several time points by spectrofluorimetry in blood and by laser scanning microscopy in muscle, liver, and tumor tissues. The boron content in the same samples was determined by mass spectroscopy with inductively coupled plasma. Results: Analysis of a linear approximation between the fluorescence intensity and boron content in the tissues demonstrated a satisfactory value of approximation reliability with a Spearman’s rank correlation coefficient of r = 0.938, p < 0.01. The dynamics of the boron concentration change in various organs, calculated on the basis of the fluorescence intensity, enabled the development of a model describing the accumulation of the studied compound and its distribution in tissues. The obtained results reveal a high level of correspondence between the model and experimental data.

Cobalt Bis-Dicarbollide Enhances Antibiotics Action towards Staphylococcus epidermidis Planktonic Growth Due to Cell Envelopes Disruption

“…These substances dispose of many important properties such as chemical and thermal stability [ 17 ], rigid geometry, delocalized negative charge, ion-pairing behavior [ 18 ], strong acidity of their conjugated acids [ 19 ], solubility in water and oils [ 20 ], ability to self-assembly into monolayer spherical nano-vesicles [ 21 , 22 ], non-specific interaction with the protein surface and high affinity to albumin [ 23 , 24 ]. The most studied area of application for heteroboranes in biological sciences is boron neutron capture therapy used for the treatment of locally invasive malignant tumors [ 23 , 25 , 26 ]. In addition, these substances have proven capability to inhibit some liver microsomal enzymes [ 27 ].…”

Chemistry of Carbon-Substituted Derivatives of Cobalt Bis(dicarbollide)(1−) Ion and Recent Progress in Boron Substitution

“…Furthermore, a mathematical model was developed that accurately describes the accumulation and distribution of CCDC in tissues. The model's high fit with the experimental data suggests its reliability and usefulness in understanding and predicting the behavior of boron accumulation and distribution in various organs [217].…”

Multi-Functional Boron-Delivery Agents for Boron Neutron Capture Therapy of Cancers

“…These compounds exhibited high phototoxicity in human lung A549 cells upon light irradiation [ 51 ]. Studies in tumor-bearing mice showed that compound 15 accumulated preferentially in the tumor with a T/N ratio of about 3:1, 3 h after IV injection of the sensitizers [ 52 ].…”