International Journal of Molecular Sciences

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16 pages, 2074 KiB

Open AccessArticle

Laser-Synthesized Elemental Boron Nanoparticles for Efficient Boron Neutron Capture Therapy

by Irina N. Zavestovskaya, Anna I. Kasatova, Dmitry A. Kasatov, Julia S. Babkova, Ivan V. Zelepukin, Ksenya S. Kuzmina, Gleb V. Tikhonowski, Andrei I. Pastukhov, Kuder O. Aiyyzhy, Ekaterina V. Barmina, Anton A. Popov, Ivan A. Razumov, Evgenii L. Zavjalov, Maria S. Grigoryeva, Sergey M. Klimentov, Vladimir A. Ryabov, Sergey M. Deyev, Sergey Yu. Taskaev and Andrei V. Kabashin

Int. J. Mol. Sci. 2023, 24(23), 17088; https://doi.org/10.3390/ijms242317088 - 4 Dec 2023

Cited by 5 | Viewed by 1850

Abstract

Boron neutron capture therapy (BNCT) is one of the most appealing radiotherapy modalities, whose localization can be further improved by the employment of boron-containing nanoformulations, but the fabrication of biologically friendly, water-dispersible nanoparticles (NPs) with high boron content and favorable physicochemical characteristics still [...] Read more.

Boron neutron capture therapy (BNCT) is one of the most appealing radiotherapy modalities, whose localization can be further improved by the employment of boron-containing nanoformulations, but the fabrication of biologically friendly, water-dispersible nanoparticles (NPs) with high boron content and favorable physicochemical characteristics still presents a great challenge. Here, we explore the use of elemental boron (B) NPs (BNPs) fabricated using the methods of pulsed laser ablation in liquids as sensitizers of BNCT. Depending on the conditions of laser-ablative synthesis, the used NPs were amorphous (a-BNPs) or partially crystallized (pc-BNPs) with a mean size of 20 nm or 50 nm, respectively. Both types of BNPs were functionalized with polyethylene glycol polymer to improve colloidal stability and biocompatibility. The NPs did not initiate any toxicity effects up to concentrations of 500 µg/mL, based on the results of MTT and clonogenic assay tests. The cells with BNPs incubated at a ¹⁰B concentration of 40 µg/mL were then irradiated with a thermal neutron beam for 30 min. We found that the presence of BNPs led to a radical enhancement in cancer cell death, namely a drop in colony forming capacity of SW-620 cells down to 12.6% and 1.6% for a-BNPs and pc-BNPs, respectively, while the relevant colony-forming capacity for U87 cells dropped down to 17%. The effect of cell irradiation by neutron beam uniquely was negligible under these conditions. Finally, to estimate the dose and regimes of irradiation for future BNCT in vivo tests, we studied the biodistribution of boron under intratumoral administration of BNPs in immunodeficient SCID mice and recorded excellent retention of boron in tumors. The obtained data unambiguously evidenced the effect of a neutron therapy enhancement, which can be attributed to efficient BNP-mediated generation of α-particles. Full article

(This article belongs to the Special Issue Latest Advances on Nanoparticles for Modern Biomedicine)

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18 pages, 5593 KiB

Open AccessArticle

Nanocomposite Materials Based on Polylactide and Gold Complex Compounds for Absorbed Dose Diagnostics in BNCT

by Vladislav Potseleev, Sergey Uspenskii, Elena Trofimchuk, Anastasia Bolshakova, Anna Kasatova, Dmitrii Kasatov and Sergey Taskaev

Int. J. Mol. Sci. 2023, 24(22), 16492; https://doi.org/10.3390/ijms242216492 - 18 Nov 2023

Viewed by 1359

Abstract

In this study, approaches to the synthesis of complex compound of gold with cysteine [AuCys]_n for measuring absorbed dose in boron neutron capture therapy (BNCT) were developed. The dependence of the complex particle size on pH were established. Nanocomposite materials based on [...] Read more.

In this study, approaches to the synthesis of complex compound of gold with cysteine [AuCys]_n for measuring absorbed dose in boron neutron capture therapy (BNCT) were developed. The dependence of the complex particle size on pH were established. Nanocomposite materials based on polylactide containing [AuCys]_n particles with an average size of about 20 nm were obtained using the crazing mechanism. The structure of obtained materials was studied by electron microscopy. The release kinetics of [AuCys]_n from polymer matrix were investigated. Release of [AuCys]_n from the volume of the polymeric matrix had a delayed start—this process began only after 24 h and was characterized by an effective rate constant of 1 μg/h from a 20 mg composite sample. At the same time, in vitro studies showed that the concentration of 6.25 μg/mL was reliably safe and did not reduce the survival of U251 and SW-620 cells. Full article

(This article belongs to the Special Issue Latest Advances on Nanoparticles for Modern Biomedicine)

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12 pages, 3971 KiB

Open AccessArticle

Transformation of Nano-Size Titanium Dioxide Particles in the Gastrointestinal Tract and Its Role in the Transfer of Nanoparticles through the Intestinal Barrier

by M. S. Ryabtseva, S. F. Umanskaya, M. A. Shevchenko, V. S. Krivobok, A. V. Kolobov, A. A. Nastulyavichus, S. I. Chentsov and V. D. Sibirtsev

Int. J. Mol. Sci. 2023, 24(19), 14911; https://doi.org/10.3390/ijms241914911 - 5 Oct 2023

Cited by 1 | Viewed by 1178

Abstract

In this work, the size transformation of the TiO₂ nanofraction from pharmaceutical grade E171 powder was studied during its transit through the gastrointestinal tract (GIT). It was shown that pharmaceutical-grade TiO₂ powder contained about 0.68% (w/w) of [...] Read more.

In this work, the size transformation of the TiO₂ nanofraction from pharmaceutical grade E171 powder was studied during its transit through the gastrointestinal tract (GIT). It was shown that pharmaceutical-grade TiO₂ powder contained about 0.68% (w/w) of particles smaller than 240 nm in diameter. In the observed GIT transit process the TiO₂ nanoparticles were agglomerated up to 150–200 nm in simulated salivary fluid, with gradual agglomerate enlargement up to 300–600 nm and more than 1 micron in simulated gastric fluid. In the intestinal fluid the reverse process occurred, involving a decrease of agglomerates accompanied by the formation of a small fraction with ~50 nm average size. This fraction can be further involved in the histohematic transport process. The acidity degree (pH) and mineral composition of solutions, as well as the transit speed along the gastrointestinal tract, influence the nature of the particle transformation significantly. The rapid passing between the gastrointestinal tract sections creates conditions for a decrease in part of the TiO₂ particles, up to 100 nm, and may be associated with the violation of the structural and functional integrity of the intestinal mucus layer. Full article

(This article belongs to the Special Issue Latest Advances on Nanoparticles for Modern Biomedicine)

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13 pages, 3474 KiB

Open AccessArticle

Molecular Dynamics Modeling of Pulsed Laser Fragmentation of Solid and Porous Si Nanoparticles in Liquid Media

by Irina A. Kutlubulatova, Maria S. Grigoryeva, Veronika A. Dimitreva, Stanislav Yu. Lukashenko, Andrey P. Kanavin, Viktor Yu. Timoshenko and Dmitry S. Ivanov

Int. J. Mol. Sci. 2023, 24(19), 14461; https://doi.org/10.3390/ijms241914461 - 23 Sep 2023

Viewed by 1415

Abstract

The production of non-toxic and homogeneous colloidal solutions of nanoparticles (NPs) for biomedical applications is of extreme importance nowadays. Among the various methods for generation of NPs, pulsed laser ablation in liquids (PLAL) has proven itself as a powerful and efficient tool in [...] Read more.

The production of non-toxic and homogeneous colloidal solutions of nanoparticles (NPs) for biomedical applications is of extreme importance nowadays. Among the various methods for generation of NPs, pulsed laser ablation in liquids (PLAL) has proven itself as a powerful and efficient tool in biomedical fields, allowing chemically pure silicon nanoparticles to be obtained. For example, laser-synthesized silicon nanoparticles (Si NPs) are widely used as contrast agents for bio visualization, as effective sensitizers of radiofrequency hyperthermia for cancer theranostics, in photodynamic therapy, as carriers of therapeutic radionuclides in nuclear nanomedicine, etc. Due to a number of complex and interrelated processes involved in the laser ablation phenomenon, however, the final characteristics of the resulting particles are difficult to control, and the obtained colloidal solutions frequently have broad and multimodal size distribution. Therefore, the subsequent fragmentation of the obtained NPs in the colloidal solutions due to pulsed laser irradiation can be utilized. The resulting NPs’ characteristics, however, depend on the parameters of laser irradiation as well as on the irradiated material and surrounding media properties. Thus, reliable knowledge of the mechanism of NP fragmentation is necessary for generation of a colloidal solution with NPs of predesigned properties. To investigate the mechanism of a laser-assisted NP fragmentation process, in this work, we perform a large-scale molecular dynamics (MD) modeling of FS laser interaction with colloidal solution of Si NPs. The obtained NPs are then characterized by their shape and morphological properties. The corresponding conclusion about the relative input of the properties of different laser-induced processes and materials to the mechanism of NP generation is drawn. Full article

(This article belongs to the Special Issue Latest Advances on Nanoparticles for Modern Biomedicine)

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13 pages, 1161 KiB

Open AccessArticle

Study of Nuclear Reactions in Therapy of Tumors with Proton Beams

by Maxim Azarkin, Martin Kirakosyan and Vladimir Ryabov

Int. J. Mol. Sci. 2023, 24(17), 13400; https://doi.org/10.3390/ijms241713400 - 29 Aug 2023

Cited by 6 | Viewed by 1553

Abstract

This paper presents an assessment of nuclear reaction yields of protons,

α

-particles, and neutrons in human tissue-equivalentmaterial in proton therapy using a simulation with Geant 4. In this study, we also check an enhancement of nuclear reactions due to the presence [...] Read more.

This paper presents an assessment of nuclear reaction yields of protons,

α

-particles, and neutrons in human tissue-equivalentmaterial in proton therapy using a simulation with Geant 4. In this study, we also check an enhancement of nuclear reactions due to the presence of Bi, Au,

^{11}

B, and

^{10}

B radiosensitizer nanoparticles. We demonstrate that a proton beam induces a noticeable amount of nuclear reactions in the tissue. Nevertheless, the enhancement of nuclear reaction products due to radiosensitizer nanoparticles is found to be negligible. Full article

(This article belongs to the Special Issue Latest Advances on Nanoparticles for Modern Biomedicine)

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15 pages, 2135 KiB

Open AccessArticle

Triangular Silver Nanoplates as a Bioanalytical Tool: Potential COVID-19 Detection

by Laura G. Rodriguez Barroso, Eduardo Lanzagorta Garcia, Marija Mojicevic, Buket Alkan Tas, Miriam Huerta, Robert Pogue, Declan M. Devine and Margaret Brennan-Fournet

Int. J. Mol. Sci. 2023, 24(15), 11974; https://doi.org/10.3390/ijms241511974 - 26 Jul 2023

Viewed by 1094

Abstract

Nanotechnology offers new possibilities in molecular diagnostics, with nanoparticles gaining attention as biosensor upgrades. This study evaluates gold-coated silver nanoplates coated with PEG for enhanced protection, aiming to detect Spike protein with higher sensitivity, and emphasizes the importance of considering complex environments and [...] Read more.

Nanotechnology offers new possibilities in molecular diagnostics, with nanoparticles gaining attention as biosensor upgrades. This study evaluates gold-coated silver nanoplates coated with PEG for enhanced protection, aiming to detect Spike protein with higher sensitivity, and emphasizes the importance of considering complex environments and appropriate controls for specific binding and accurate analysis. The sensitivity of antibody-coated PEGAuTSNPs as tools for immunoassays is demonstrated through fibronectin (Fn)– anti-fibronectin binding within an isolated extracellular matrix as a complex and native environment of Fn. Moreover, the optimal functionalization volume of Spike protein was determined (4 µg/mL of PEGAuTSNP). Anti-Spike was added to confirm binding, while the TJP1 protein was used as a negative control. The same experiment was used in the presence of horse serum to simulate a complex environment. According to Localized Surface Plasmon Resonance analysis and Dynamic Light Scattering size measurements, anti-Spike exhibited a stronger affinity for the nanoplates, causing TJP1 to be replaced by the antibody on the nanoplates’ surface. Future research will involve exploring alternative complex environments, filtering larger molecules, and the optimization of immunoassay performance. Full article

(This article belongs to the Special Issue Latest Advances on Nanoparticles for Modern Biomedicine)

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17 pages, 1925 KiB

Open AccessArticle

Optimization of Size of Nanosensitizers for Antitumor Radiotherapy Using Mathematical Modeling

by Maxim Kuznetsov and Andrey Kolobov

Int. J. Mol. Sci. 2023, 24(14), 11806; https://doi.org/10.3390/ijms241411806 - 22 Jul 2023

Cited by 5 | Viewed by 1208

Abstract

The efficacy of antitumor radiotherapy can be enhanced by utilizing nonradioactive nanoparticles that emit secondary radiation when activated by a primary beam. They consist of small volumes of a radiosensitizing substance embedded within a polymer layer, which is coated with tumor-specific antibodies. The [...] Read more.

The efficacy of antitumor radiotherapy can be enhanced by utilizing nonradioactive nanoparticles that emit secondary radiation when activated by a primary beam. They consist of small volumes of a radiosensitizing substance embedded within a polymer layer, which is coated with tumor-specific antibodies. The efficiency of nanosensitizers relies on their successful delivery to the tumor, which depends on their size. Increasing their size leads to a higher concentration of active substance; however, it hinders the penetration of nanosensitizers through tumor capillaries, slows down their movement through the tissue, and accelerates their clearance. In this study, we present a mathematical model of tumor growth and radiotherapy with the use of intravenously administered tumor-specific nanosensitizers. Our findings indicate that their optimal size for achieving maximum tumor radiosensitization following a single injection of their fixed total volume depends on the permeability of the tumor capillaries. Considering physiologically plausible spectra of capillary pore radii, with a nanoparticle polymer layer width of 7 nm, the optimal radius of nanoparticles falls within the range of 13–17 nm. The upper value is attained when considering an extreme spectrum of capillary pores. Full article

(This article belongs to the Special Issue Latest Advances on Nanoparticles for Modern Biomedicine)

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Review

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15 pages, 2705 KiB

Open AccessReview

The Role of Carbon Nanoparticles as Lymph Node Tracers in Colorectal Cancer: A Systematic Review and Meta-Analysis

by Georgios Koimtzis, Georgios Geropoulos, Leandros Stefanopoulos, Christopher Gwydion Chalklin, Ioannis Karniadakis, Vyron Alexandrou, Nikos Tteralli, Eliot Carrington-Windo, Andreas Papacharalampous and Kyriakos Psarras

Int. J. Mol. Sci. 2023, 24(20), 15293; https://doi.org/10.3390/ijms242015293 - 18 Oct 2023

Cited by 2 | Viewed by 1597

Abstract

Colorectal malignancies are the third-most common malignancies worldwide, with a rising incidence. Surgery remains the treatment of choice and adequate lymph node dissection is required for accurate staging. The objective of this study is to assess the use of carbon nanoparticles in lymph [...] Read more.

Colorectal malignancies are the third-most common malignancies worldwide, with a rising incidence. Surgery remains the treatment of choice and adequate lymph node dissection is required for accurate staging. The objective of this study is to assess the use of carbon nanoparticles in lymph node tracing and resection in cases of colorectal cancer. For that purpose, we conducted a systematic review and meta-analysis of studies included in Medline, Scopus, Embase, Cochrane Library, and Google Scholar databases. In the end, ten studies with a total number of 1418 patients were included in the final statistical analysis. The meta-analysis carried out showed that the use of carbon nanoparticles results in an increased number of lymph nodes harvested (WMD 6.15, 95% CI 4.14 to 8.16, p < 0.001) and a higher rate of cases with more than 12 lymph nodes harvested (OR 9.57, 95% CI 2.87 to 31.96, p = 0.0002). As a consequence, we suggest that carbon nanoparticles are used on a wider scale and that future research focuses on assessing the association between their use and overall patient survival. This study is limited by the fact that all included studies originate from China and by the fact that certain oncologic parameters and long-term outcomes have not been taken into account in the analysis. Full article

(This article belongs to the Special Issue Latest Advances on Nanoparticles for Modern Biomedicine)

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