The Endocytic Mechanism and Cytotoxicity of Boron-Containing Vesicles

Abstract

A novel polymer (PEG 2000-carborane), self-assembling into spherical vesicles (boron-containing vesicles, BCVs), could be quickly taken up by tumor cells and had an enhance stability in the bloodstream in previous study. To have more comprehensive understanding of BCVs, endocytic mechanism and cytotoxicity assessment were conducted. The results showed that BCVs were taken up in the intact form with cholesteroldependent pathway during endocytosis, and BCVs exhibited nearly no cytotoxicity. BCVs could accumulate within tumors for at least 24 h. The data would provide reference information and guidance for BCVs' multifunctional application serving as a boron delivery agent for boron neutron capture therapy (BNCT), a hydrophilic and/or hydrophobic drug carrier and a diagnostic imaging fluorescent probe.

Physical bases of Boron Neutron Capture Therapy, Dosimetry, and Its Mechanisms of Action - Critical Overview of the Literature

“…To solve this problem and achieve selective tumor accumulation and reduced toxicity, several approaches like coating, functionalizing, and many others have also been applied. Labeling by different fluorophores or molecules with fluorescence properties was also researched and developed for better imaging [15,16].…”

“…Human tissue also contains certain isotopes that react with neutrons. Due to the values of nuclear cross-sections, most meaningful interactions of neutrons with human tissue involve 1 H, 12 C, 14 N, and 16 O isotopes, which account for 99.2% of all atoms in the human body [35]. The types of occurring DNA lesions -base damage, crosslinks DNA-protein or DNA-DNA, double-strand breaks (DSB), single-strand break (SSB), sugar-phosphate backbone interruption etc.…”

“…Several modalities are widely used to assess boron dose delivered to the residual tumor volume, and they can provide information about the 10 B distribution at the microscopic level [12,13]. To improve molecular imaging, several approaches have been proposed [14][15][16][17]. Another critical issue is developing treatment planning programs and systems to calculate the dose, predict the particle fluxes and expect the incidence angles on the patients to achieve the adequate relative dose distribution.…”

Boron neutron capture therapy: Current status and future perspectives

“…One of the problems that nuclear doctors face when using neutron irradiation is the lack of a quantitative imaging method for evaluation of the boron concentration. To solve this problem and to achieve selective tumor accumulation and reduced toxicity, several approaches have been applied: (1) coating of boronated porphyrins with biocompatible poly(lactide-co-glycolide)monomethoxypoly(polyethylene-glycol) (PLGA-mPEG) micelles [43], functionalizing mesoporous silica nanoparticles [51], labeling MMT1242 with a nitrobenzoxadiazole frame, which emits green-yellow fluorescence [52], and so on, in general, labeling vesicles by different fluorophores or molecules with fluorescence properties [53,54]. Ion microscopy may also be used to evaluate the distribution of isotope 10 B, as was shown in two brain tumor models, the 9L rat gliosarcoma and the F98 rat glioma [55].…”

Physical Bases of Boron Neutron Capture Therapy, Dosimetry, and Its Mechanisms of Action—A Critical Overview of the Literature

“…Several modalities are widely used to assess the boron dose delivered to the residual tumor volume, and they can provide information on the distribution of 10 B at the microscopic level [11,12]. To improve molecular imaging, several other approaches have been proposed [13][14][15]. Another critical issue is developing treatment planning programs and systems to calculate the dose, predict the particle fluxes, and expect the incidence angles on the patients to achieve the adequate relative dose distribution.…”