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1.
Bull Exp Biol Med ; 176(5): 626-630, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38730109

RESUMO

We studied the antitumor activity of the combined use of local proton irradiation in two modes (10 and 31 Gy) with preliminary intra-tumoral injection of two types of bismuth nanoparticles differing in surface coating: coated with the amphiphilic molecule Pluronic-F127 or Silane-PEG (5 kDa)-COOH polymer. Nanoparticles were used in doses of 0.75 and 1.5 mg/mouse. In two independent series on experimental tumor model (solid Ehrlich carcinoma), bismuth nanoparticles of both modifications injected directly into the tumor enhanced the antitumor effects of proton therapy. Moreover, the radiosensitizing effect of bismuth nanoparticles administered via this route increased with the increasing the doses of nanoparticles and the doses of radiation exposure. In our opinion, these promising data obtained for the first time extend the possibilities of treating malignant neoplasms.


Assuntos
Bismuto , Carcinoma de Ehrlich , Poloxâmero , Terapia com Prótons , Carcinoma de Ehrlich/radioterapia , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Animais , Bismuto/uso terapêutico , Bismuto/química , Camundongos , Terapia com Prótons/métodos , Poloxâmero/química , Radiossensibilizantes/uso terapêutico , Radiossensibilizantes/química , Radiossensibilizantes/farmacologia , Polietilenoglicóis/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Nanopartículas/química , Feminino
2.
Biomed Pharmacother ; 175: 116668, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701565

RESUMO

The combination of radiation treatment and chemotherapy is currently the standard for management of cancer patients. However, safe doses do not often provide effective therapy, then pre-treated patients are forced to repeat treatment with often already increased tumor resistance to drugs and irradiation. One of the solutions we suggest is to improve primary course of radiation treatment via enhancing radiosensitivity of tumors by magnetic-guided iron oxide nanoparticles (magnetite). We obtained spherical heparinized iron oxide nanoparticles (hIONPs, ∼20 nm), characterized it by TEM, Infrared spectroscopy and DLS. Then hIONPs cytotoxicity was assessed for colon cancer cells (XTT assay) and cellular uptake of nanoparticles was analyzed with X-ray fluorescence. Combination of ionizing radiation (IR) and hIONPs in vitro caused an increase of G2/M arrest of cell cycle, mitotic errors and decrease in survival (compared with samples exposed to IR and hIONPs separately). The promising results were shown for magnetic-guided hIONPs in CT26-grafted BALB/C mice: the combination of intravenously administrated hIONPs and IR showed 20,8% T/C ratio (related to non-treated mice), while single radiation had no shown significant decrease in tumor growth (72,4%). Non-guided by magnets hIONPs with IR showed 57,9% of T/C. This indicates that ultra-small size and biocompatible molecule are not the key to successful nano-drug design, in each case, delivery technologies need to be improved when transferred to in vivo model.


Assuntos
Neoplasias do Colo , Heparina , Nanopartículas Magnéticas de Óxido de Ferro , Camundongos Endogâmicos BALB C , Radiossensibilizantes , Animais , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/radioterapia , Nanopartículas Magnéticas de Óxido de Ferro/química , Radiossensibilizantes/farmacologia , Radiossensibilizantes/química , Radiossensibilizantes/administração & dosagem , Humanos , Camundongos , Linhagem Celular Tumoral , Heparina/química , Heparina/farmacologia , Nanopartículas de Magnetita/química , Ensaios Antitumorais Modelo de Xenoenxerto , Sobrevivência Celular/efeitos dos fármacos
3.
J Nanobiotechnology ; 22(1): 234, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724978

RESUMO

Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide (HfO2) that was core coated with a MnO2 shell followed by a glucose oxidase (GOx) doping nanoplatform (HfO2@MnO2@GOx, HMG) to trigger ferroptosis adjuvant effects by glutathione depletion and reactive oxygen species production. This ferroptosis cascade potentiation further sensitized radiotherapy by enhancing DNA damage in 4T1 breast cancer tumor cells. The combination of HMG nanoparticles and radiotherapy effectively activated the damaged DNA and Mn2+-mediated cGAS-STING immune pathway in vitro and in vivo. This process had significant inhibitory effects on cancer progression and initiating an anticancer systemic immune response to prevent distant tumor recurrence and achieve long-lasting tumor suppression of both primary and distant tumors. Furthermore, the as-prepared HMG nanoparticles "turned on" spectral computed tomography (CT)/magnetic resonance dual-modality imaging signals, and demonstrated favorable contrast enhancement capabilities activated by under the GSH tumor microenvironment. This result highlighted the potential of nanoparticles as a theranostic nanoplatform for achieving molecular imaging guided tumor radiotherapy sensitization induced by synergistic immunotherapy.


Assuntos
Ferroptose , Imunoterapia , Compostos de Manganês , Proteínas de Membrana , Camundongos Endogâmicos BALB C , Nanopartículas , Nucleotidiltransferases , Óxidos , Radiossensibilizantes , Animais , Camundongos , Imunoterapia/métodos , Óxidos/química , Óxidos/farmacologia , Feminino , Nucleotidiltransferases/metabolismo , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Linhagem Celular Tumoral , Nanopartículas/química , Radiossensibilizantes/farmacologia , Radiossensibilizantes/química , Proteínas de Membrana/metabolismo , Ferroptose/efeitos dos fármacos , Glucose Oxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Humanos , Dano ao DNA , Microambiente Tumoral/efeitos dos fármacos
4.
ACS Appl Mater Interfaces ; 16(17): 21557-21570, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38648555

RESUMO

We report the synthesis of biocompatible perfluorinated micelles designed to improve radiotherapeutic efficacy in a radioresistant tumor environment. In vitro and in vivo behaviors of perfluorinated micelles were assessed at both cellular and tissular levels. The micellar platform offers key advantages as theranostic tool: (i) small size, allowing deep tissue penetration; (ii) oxygen transport to hypoxic tissues; (iii) negligible toxicity in the absence of ionizing radiation; (iv) internalization into cancer cells; (v) potent radiosensitizing effect; and (vi) excellent tumor-targeting properties, as monitored by positron emission tomography. We have demonstrated strong in vitro radiosensitizing effects of the micelle and in vivo tumor targeting, making this nanometric carrier a promising tool for the potentiation of focused radiotherapy.


Assuntos
Micelas , Tomografia por Emissão de Pósitrons , Radiossensibilizantes , Nanomedicina Teranóstica , Animais , Humanos , Radiossensibilizantes/química , Radiossensibilizantes/farmacologia , Radiossensibilizantes/síntese química , Camundongos , Linhagem Celular Tumoral , Fluorocarbonos/química , Fluorocarbonos/farmacologia , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia
5.
Adv Mater ; 36(19): e2312588, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38316447

RESUMO

Cancer cells can upregulate the MYC expression to repair the radiotherapy-triggered DNA damage, aggravating therapeutic resistance and tumor immunosuppression. Epigenetic treatment targeting the MYC-transcriptional abnormality may intensively solve this clinical problem. Herein, 5-Aza (a DNA methyltransferase inhibitor) and ITF-2357 (a histone deacetylase inhibitor) are engineered into a tungsten-based nano-radiosensitizer (PWAI), to suppress MYC rising and awaken robust radiotherapeutic antitumor immunity. Individual 5-Aza depletes MYC expression but cannot efficiently awaken radiotherapeutic immunity. This drawback can be overcome by the addition of ITF-2357, which triggers cancer cellular type I interferon (IFN-I) signaling. Coupling 5-Aza with ITF-2357 ensures that PWAI does not evoke the treated model with high MYC-related immune resistance while amplifying the radiotherapeutic tumor killing, and more importantly promotes the generation of IFN-I signal-related proteins involving IFN-α and IFN-ß. Unlike the radiation treatment alone, PWAI-triggered immuno-radiotherapy remarkably enhances antitumor immune responses involving the tumor antigen presentation by dendritic cells, and improves intratumoral recruitment of cytotoxic T lymphocytes and their memory-phenotype formation in 4T1 tumor-bearing mice. Downgrading the radiotherapy-induced MYC overexpression via the dual-epigenetic reprogramming strategy may elicit a robust immuno-radiotherapy.


Assuntos
Epigênese Genética , Imunoterapia , Proteínas Proto-Oncogênicas c-myc , Radiossensibilizantes , Animais , Camundongos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Epigênese Genética/efeitos dos fármacos , Linhagem Celular Tumoral , Radiossensibilizantes/farmacologia , Radiossensibilizantes/química , Radiossensibilizantes/uso terapêutico , Nanopartículas/química , Humanos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Neoplasias/terapia , Neoplasias/imunologia , Terapia de Imunossupressão , Interferon Tipo I/metabolismo
6.
Adv Mater ; 36(23): e2314132, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38353332

RESUMO

Radiation therapy (RT) is one of the primary options for clinical cancer therapy, in particular advanced head and neck squamous cell carcinoma (HNSCC). Herein, the crucial role of bromodomain-containing protein 4 (BRD4)-RAD51 associated protein 1 (RAD51AP1) axis in sensitizing RT of HNSCC is revealed. A versatile nanosensitizer (RPB7H) is thus innovatively engineered by integrating a PROteolysis TArgeting Chimeras (PROTAC) prodrug (BPA771) and hafnium dioxide (HfO2) nanoparticles to downregulate BRD4-RAD51AP1 pathway and sensitize HNSCC tumor to RT. Upon intravenous administration, the RPB7H nanoparticles selectively accumulate at the tumor tissue and internalize into tumor cells by recognizing neuropilin-1 overexpressed in the tumor mass. HfO2 nanoparticles enhance RT effectiveness by amplifying X-ray deposition, intensifying DNA damage, and boosting oxidative stress. Meanwhile, BPA771 can be activated by RT-induced H2O2 secretion to degrade BRD4 and inactivate RAD51AP1, thus impeding RT-induced DNA damage repair. This versatile nanosensitizer, combined with X-ray irradiation, effectively regresses HNSCC tumor growth in a mouse model. The findings introduce a PROTAC prodrug-based radiosensitization strategy by targeting the BRD4-RAD51AP1 axis, may offer a promising avenue to augment RT and more effective HNSCC therapy.


Assuntos
Nanopartículas , Pró-Fármacos , Radiossensibilizantes , Fatores de Transcrição , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Animais , Humanos , Linhagem Celular Tumoral , Camundongos , Radiossensibilizantes/química , Radiossensibilizantes/farmacologia , Fatores de Transcrição/metabolismo , Nanopartículas/química , Proteínas de Ciclo Celular/metabolismo , Proteólise/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Dano ao DNA/efeitos dos fármacos , Neuropilina-1/metabolismo , Proteínas que Contêm Bromodomínio
7.
Adv Healthc Mater ; 13(14): e2303626, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38387885

RESUMO

Immunotherapy has emerged as an innovative strategy with the potential to improve outcomes in cancer patients. Recent evidence indicates that radiation-induced DNA damage can activate the cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to enhance the antitumor immune response. Even so, only a small fraction of patients currently benefits from radioimmunotherapy due to the radioresistance and the inadequate activation of the cGAS-STING pathway. Herein, this work integrates hafnium oxide (HfO2) nanoparticles (radiosensitizer) and 7-Ethyl-10-hydroxycamptothecin (SN38, chemotherapy drug, STING agonist) into a polydopamine (PDA)-coated core-shell nanoplatform (HfO2@PDA/Fe/SN38) to achieve synergistic chemoradiotherapy and immunotherapy. The co-delivery of HfO2/SN38 greatly enhances radiotherapy efficacy by effectively activating the cGAS-STING pathway, which then triggers dendritic cells maturation and CD8+ T cells recruitment. Consequently, the growth of both primary and abscopal tumors in tumor-bearing mice is efficiently inhibited. Moreover, the HfO2@PDA/Fe/SN38 complexes exhibit favorable magnetic resonance imaging (MRI)/photoacoustic (PA) bimodal molecular imaging properties. In summary, these developed multifunctional complexes have the potential to intensify immune activation to realize simultaneous cancer Radio/Chemo/Immunotherapy for clinical translation.


Assuntos
Imunoterapia , Proteínas de Membrana , Nanopartículas , Nucleotidiltransferases , Animais , Nucleotidiltransferases/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Imunoterapia/métodos , Nanopartículas/química , Radiossensibilizantes/química , Radiossensibilizantes/farmacologia , Linhagem Celular Tumoral , Humanos , Camptotecina/farmacologia , Camptotecina/química , Camptotecina/análogos & derivados , Imagem Molecular/métodos , Polímeros/química , Neoplasias/terapia , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Feminino
8.
Adv Mater ; 36(23): e2311291, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38408154

RESUMO

Radiotherapy, a widely used therapeutic strategy for esophageal squamous cell carcinoma (ESCC), is always limited by radioresistance of tumor tissues and side-effects on normal tissues. Herein, a signature based on four core genes of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is developed to predict prognosis and assess immune cell infiltration, indicating that the cGAS-STING pathway and radiotherapy efficacy are closely intertwined in ESCC. A novel lipid-modified manganese diselenide nanoparticle (MnSe2-lipid) with extraordinarily uniform sphere morphology and tumor microenvironment (TME) responsiveness is developed to simultaneously overcome radioresistance and reduce side-effects of radiation. The uniform MnSe2 encapsulated lipid effectively achieves tumor accumulation. Octadecyl gallate on surface of MnSe2 forming pH-responsive metal-phenolic covalent realizes rapid degradation in TME. The released Mn2+ promotes radiosensitivity by generating reactive oxygen species induced by Fenton-like reaction and activating cGAS-STING pathway. Spontaneously, selenium strengthens immune response by promoting secretion of cytokines and increasing white blood cells, and performs antioxidant activity to reduce side-effects of radiotherapy. Overall, this multifunctional remedy which is responsive to TME is capable of providing radiosensitivity by cGAS-STING pathway-mediated immunostimulation and chemodynamic therapy, and radioprotection of normal tissues, is highlighted here to optimize ESCC treatment.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Nanopartículas , Tolerância a Radiação , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Animais , Nanopartículas/química , Linhagem Celular Tumoral , Camundongos , Ácido Gálico/química , Ácido Gálico/farmacologia , Ácido Gálico/análogos & derivados , Lipídeos/química , Selênio/química , Selênio/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Protetores contra Radiação/farmacologia , Protetores contra Radiação/química , Manganês/química , Radiossensibilizantes/química , Radiossensibilizantes/farmacologia
9.
Phys Chem Chem Phys ; 26(11): 8761-8766, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38419552

RESUMO

5-Fluorouracil is now routinely used in chemo- and radiotherapy. Incorporated within DNA, the molecule is bound to the sugar backbone, forming the 5-fluorouridine sub-unit investigated in the present work. For the clinical usage of the latter, no information exists on the mechanisms that control the radiosensitizing effect at the molecular level. As low energy (< 12 eV) electrons are abundantly produced along the radiation tracks during cancer treatment using beams of high energy particles, we study how these ballistic secondary electrons damage the sensitizing molecule. The salient result from our study shows that the N-glycosidic bonds are principally affected with a cross-section of approximately two orders of magnitude higher than the canonical thymidine, reflecting to some degree the surviving factor of radiation-treated carcinoma cells with and without 5-fluorouracil incorporation. This result may help in the comprehension of the radiosensitizing effect of the fluoro-substituted thymidine in DNA.


Assuntos
Elétrons , Radiossensibilizantes , Uridina/análogos & derivados , DNA/química , Radiossensibilizantes/química , Dano ao DNA , Timidina , Fluoruracila
10.
Phys Med Biol ; 69(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38286017

RESUMO

Objective. Gold nanorods (GNRs) have emerged as versatile nanoparticles with unique properties, holding promise in various modalities of cancer treatment through drug delivery and photothermal therapy. In the rapidly evolving field of nanoparticle radiosensitization (NPRS) for cancer therapy, this study assessed the potential of gold nanorods as radiosensitizing agents by quantifying the key features of NPRS, such as secondary electron emission and dose enhancement, using Monte Carlo simulations.Approach. Employing the TOPAS track structure code, we conducted a comprehensive evaluation of the radiosensitization behavior of spherical gold nanoparticles and gold nanorods. We systematically explored the impact of nanorod geometry (in particular size and aspect ratio) and orientation on secondary electron emission and deposited energy ratio, providing validated results against previously published simulations.Main results. Our findings demonstrate that gold nanorods exhibit comparable secondary electron emission to their spherical counterparts. Notably, nanorods with smaller surface-area-to-volume ratios (SA:V) and alignment with the incident photon beam proved to be more efficient radiosensitizing agents, showing superiority in emitted electron fluence. However, in the microscale, the deposited energy ratio (DER) was not markedly influenced by the SA:V of the nanorod. Additionally, our findings revealed that the geometry of gold nanoparticles has a more significant impact on the emission of M-shell Auger electrons (with energies below 3.5 keV) than on higher-energy electrons.Significance. This research investigated the radiosensitization properties of gold nanorods, positioning them as promising alternatives to the more conventionally studied spherical gold nanoparticles in the context of cancer research. With increasing interest in multimodal cancer therapy, our findings have the potential to contribute valuable insights into the perspective of gold nanorods as effective multipurpose agents for synergistic photothermal therapy and radiotherapy. Future directions may involve exploring alternative metallic nanorods as well as further optimizing the geometry and coating materials, opening new possibilities for more effective cancer treatments.


Assuntos
Nanopartículas Metálicas , Nanotubos , Radiossensibilizantes , Ouro/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Radiossensibilizantes/farmacologia , Radiossensibilizantes/química , Simulação por Computador
11.
Int J Mol Sci ; 24(20)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37894830

RESUMO

The potential of standard methods of radiation therapy is limited by the dose that can be safely delivered to the tumor, which could be too low for radical treatment. The dose efficiency can be increased by using radiosensitizers. In this study, we evaluated the sensitizing potential of biocompatible iron oxide nanoparticles coated with a dextran shell in A172 and Gl-Tr glioblastoma cells in vitro. The cells preincubated with nanoparticles for 24 h were exposed to ionizing radiation (X-ray, gamma, or proton) at doses of 0.5-6 Gy, and their viability was assessed by the Resazurin assay and by staining of the surviving cells with crystal violet. A statistically significant effect of radiosensitization by nanoparticles was observed in both cell lines when cells were exposed to 35 keV X-rays. A weak radiosensitizing effect was found only in the Gl-Tr line for the 1.2 MeV gamma irradiation and there was no radiosensitizing effect in both lines for the 200 MeV proton irradiation at the Bragg peak. A slight (ca. 10%) increase in the formation of additional reactive oxygen species after X-ray irradiation was found when nanoparticles were present. These results suggest that the nanoparticles absorbed by glioma cells can produce a significant radiosensitizing effect, probably due to the action of secondary electrons generated by the magnetite core, whereas the dextran shell of the nanoparticles used in these experiments appears to be rather stable under radiation exposure.


Assuntos
Glioma , Nanopartículas Metálicas , Nanopartículas , Radiossensibilizantes , Humanos , Radiossensibilizantes/farmacologia , Radiossensibilizantes/química , Dextranos/química , Prótons , Glioma/radioterapia , Glioma/patologia , Linhagem Celular Tumoral , Nanopartículas Magnéticas de Óxido de Ferro , Nanopartículas Metálicas/química
12.
J Phys Chem Lett ; 14(40): 8948-8955, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37769041

RESUMO

In the search for effective radiosensitizers for tumor cells, halogenated uracils have attracted more attention due to their large cross section for dissociation upon the attachment of low-energy electrons. In this study, we investigated dissociative electron attachment (DEA) to 5-iodo-4-thio-2'-deoxyuridine, a potential radiosensitizer using a crossed electron-molecule beam experiment coupled with quadrupole mass spectrometry. The experimental results were supported by calculations on the threshold energies of formed anions and transition state calculations. We show that low-energy electrons with kinetic energies near 0 eV may effectively decompose the molecule upon DEA. The by far most abundant anion observed corresponds to the iodine anion (I-). Due to the associated bond cleavage, a radical site is formed at the C5 position, which may initiate strand break formation if the molecule is incorporated into a DNA strand. Our results reflect the conclusion from previous radiolysis studies with the title compound, suggesting its potential as a radiosensitizer.


Assuntos
Elétrons , Radiossensibilizantes , Radiossensibilizantes/farmacologia , Radiossensibilizantes/química , Tiouridina , Ânions
13.
IET Nanobiotechnol ; 17(4): 302-311, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37139612

RESUMO

About 50% of cancer patients receive radiation therapy. Despite the therapeutic benefits of this method, the toxicity of radiation in the normal tissues is unavoidable To improve the quality of radiation therapy, in addition to other methods such as IMRT, IGRT, and high radiation dose, nanoparticles have shown excellent potential when ionising radiation is applied to the target volume. Recently, bismuth-based nanoparticles (BiNPs) have become particularly popular in radiation therapy due to their high atomic numbers (Z), high X-ray attenuation coefficient, low toxicity, and low cost. Moreover, it is easy to synthesise in a variety of sizes and shapes. This study aimed to review the effects of the bismuth-based NP and its combination with other compounds, and their potential synergies in radiotherapy, discussed based on their physical, chemical, and biological interactions. Targeted and non-targeted bismuth-based NPs used in radiotherapy as radiosensitizers and dose enhancement effects are described. The results reported in the literature were categorised into various groups. Also, this review has highlighted the importance of bismuth-based NPs in different forms of cancer treatment to find the highest efficiency for applying them as a suitable candidate for various cancer therapy and future clinical applications.


Assuntos
Nanopartículas , Neoplasias , Radiossensibilizantes , Humanos , Bismuto/química , Nanopartículas/química , Radiossensibilizantes/química , Neoplasias/radioterapia , Neoplasias/tratamento farmacológico
14.
Artigo em Inglês | MEDLINE | ID: mdl-36987630

RESUMO

Radiotherapy is an inevitable choice for cancer treatment that is applied as combinatorial therapy along with surgery and chemotherapy. Nevertheless, radiotherapy at high doses kills normal and tumor cells at the same time. In addition, some tumor cells are resistant to radiotherapy. Recently, many researchers have focused on high-Z nanomaterials as radiosensitizers for radiotherapy. Among them, gold nanoparticles (GNPs) have shown remarkable potential due to their promising physical, chemical, and biological properties. Although few clinical trial studies have been performed on drug delivery and photosensitization with lasers, GNPs have not yet received Food and Drug Administration approval for use in radiotherapy. The sensitization effects of GNPs are dependent on their concentration in cells and x-ray energy deposition during radiotherapy. Notably, some limitations related to the properties of the GNPs, including their size, shape, surface charge, and ligands, and the radiation source energy should be resolved. At the first, this review focuses on some of the challenges of using GNPs as radiosensitizers and some biases among in vitro/in vivo, Monte Carlo, and clinical studies. Then, we discuss the challenges in the clinical translation of GNPs as radiosensitizers for radiotherapy and proposes feasible solutions. And finally, we suggest that certain areas be considered in future research. This article is categorized under: Therapeutic Approaches and Drug Discovery > NA.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , Radiossensibilizantes , Radiossensibilizantes/uso terapêutico , Radiossensibilizantes/química , Ouro/uso terapêutico , Ouro/química , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Sistemas de Liberação de Medicamentos
15.
Int J Mol Sci ; 24(5)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36902132

RESUMO

Metal nanoparticles are considered as highly promising radiosensitizers in cancer radiotherapy. Understanding their radiosensitization mechanisms is critical for future clinical applications. This review is focused on the initial energy deposition by short-range Auger electrons; when high energy radiation is absorbed by gold nanoparticles (GNPs) located near vital biomolecules; such as DNA. Auger electrons and the subsequent production of secondary low energy electrons (LEEs) are responsible for most the ensuing chemical damage near such molecules. We highlight recent progress on DNA damage induced by the LEEs produced abundantly within about 100 nanometers from irradiated GNPs; and by those emitted by high energy electrons and X-rays incident on metal surfaces under differing atmospheric environments. LEEs strongly react within cells; mainly via bound breaking processes due to transient anion formation and dissociative electron attachment. The enhancement of damages induced in plasmid DNA by LEEs; with or without the binding of chemotherapeutic drugs; are explained by the fundamental mechanisms of LEE interactions with simple molecules and specific sites on nucleotides. We address the major challenge of metal nanoparticle and GNP radiosensitization; i.e., to deliver the maximum local dose of radiation to the most sensitive target of cancer cells (i.e., DNA). To achieve this goal the emitted electrons from the absorbed high energy radiation must be short range, and produce a large local density of LEEs, and the initial radiation must have the highest possible absorption coefficient compared to that of soft tissue (e.g., 20-80 keV X-rays).


Assuntos
Nanopartículas Metálicas , Radiossensibilizantes , Nanopartículas Metálicas/química , Elétrons , Ouro/química , Radiossensibilizantes/química , DNA/química
16.
Biomater Sci ; 11(4): 1116-1136, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36601661

RESUMO

Radiotherapy (RT) is one of the most effective and commonly used cancer treatments for malignant tumors. However, the existing radiosensitizers have a lot of side effects and poor efficacy, which limits the curative effect and further application of radiotherapy. In recent years, emerging nanomaterials have shown unique advantages in enhancing radiosensitization. In particular, gold-based nanomaterials, with high X-ray attenuation capacity, good biocompatibility, and promising chemical, electronic and optical properties, have become a new type of radiotherapy sensitizer. In addition, gold-based nanomaterials can be used as a carrier to load a variety of drugs and immunosuppressants; in particular, its photothermal therapy, photodynamic therapy and multi-mode imaging functions aid in providing excellent therapeutic effect in coordination with RT. Recently, many novel strategies of radiosensitization mediated by multifunctional gold-based nanomaterials have been reported, which provides a new idea for improving the efficacy and reducing the side effects of RT. In this review, we systematically summarize the recent progress of various new gold-based nanomaterials that mediate radiosensitization and describe the mechanism. We further discuss the challenges and prospects in the field. It is hoped that this review will help researchers understand the latest progress of gold-based nanomaterials for radiosensitization, and encourage people to optimize the existing methods or explore novel approaches for radiotherapy.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , Neoplasias , Radiossensibilizantes , Humanos , Ouro/química , Nanopartículas Metálicas/química , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Radiossensibilizantes/química
17.
Small ; 19(11): e2204238, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36494177

RESUMO

Over half of cancer patients are subjected to radiotherapy, but owing to the deficient amount of reactive oxygen radicals (ROS) and DNA double-strand breaks (DSBs), a fair number of them suffer from radiotherapy resistance and the subsequent short-term survival opportunity. To overcome it, many successes have been achieved in radiosensitizer discovery using physical strategy and/or biological strategy, but significant challenges remain regarding developing clinically translational radiosensitizers. Herein, a peptide-Au(I) infinite coordination supermolecule termed PAICS is developed that combined both physical and biological radiosensitization and possessed pharmaceutical characteristics including adequate circulatory stability, controllable drug release, tumor-prioritized accumulation, and the favorable body eliminability. As expected, monovalent gold ion endowed this supermolecule with high X-ray absorption and the subsequent radiosensitization. Furthermore, a peptide targeting CRM1, is assembled into the supermolecule, which successfully activates p53 and apoptosis pathway, thereby further sensitizing radiotherapy. As a result, PAICS showed superior ability for radiotherapy sensitization in vivo and maintained a favorable safety profile. Thus, the PAICS reported here will offer a feasible solution to simultaneously overcome both the pharmaceutical obstacles of physical and biological radiosensitizers and will enable the development of a class of nanomedicines for tumor radiotherapy sensitization.


Assuntos
Nanopartículas Metálicas , Neoplasias , Radiossensibilizantes , Humanos , Radiossensibilizantes/farmacologia , Radiossensibilizantes/uso terapêutico , Radiossensibilizantes/química , Neoplasias/radioterapia , Neoplasias/tratamento farmacológico , Peptídeos , Preparações Farmacêuticas , Ouro/química , Nanopartículas Metálicas/uso terapêutico
18.
J Chem Phys ; 157(7): 074301, 2022 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-35987575

RESUMO

Fluorodeoxyglucose (FDG) is a glucose derivative with fluorine at the C2 position. The molecule containing the radioactive F-18 isotope is well known from its application in positron emission tomography as a radiotracer in tumor examination. In the stable form with the F-19 isotope, FDG was proposed as a potential radiosensitizer. Since reduction processes may be relevant in radiosensitization, we investigated low-energy electron attachment to FDG with a crossed electron-molecule beam experiment and with quantum chemical calculations as well as molecular dynamics at elevated temperatures to reveal statistical dissociation. We experimentally find that the susceptibility of FDG to low-energy electrons is relatively low. The calculations indicate that upon attachment of an electron with a kinetic energy of ∼0 eV, only dipole-bound states are accessible, which agrees with the weak ion yields observed in the experiment. The temporary negative ions formed upon electron attachment to FDG may decay by a large variety of dissociation reactions. The major fragmentation channels include H2O, HF, and H2 dissociation, accompanied by ring opening.


Assuntos
Elétrons , Radiossensibilizantes , Fluordesoxiglucose F18 , Íons , Radiossensibilizantes/química
19.
Int J Mol Sci ; 23(5)2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35269573

RESUMO

In chemoradiation therapy, dissociative electron attachment (DEA) may play an important role with respect to the efficiency of the radiosensitizers used. The rational tailoring of such radiosensitizers to be more susceptive to DEA may thus offer a path to increase their efficiency. Potentially, this may be achieved by tailoring rearrangement reactions into the DEA process such that these may proceed at low incident electron energies, where DEA is most effective. Favorably altering the orbital structure of the respective molecules through substitution is another path that may be taken to promote dissociation up on electron capture. Here we present a combined experimental and theoretical study on DEA in relation to pentafluorothiophenol (PFTP) and 2-fluorothiophenol (2-FTP). We investigate the thermochemistry and dynamics of neutral HF formation through DEA as means to lower the threshold for dissociation up on electron capture to these compounds, and we explore the influence of perfluorination on their orbital structure. Fragment ion yield curves are presented, and the thermochemical thresholds for the respective DEA processes are computed as well as the minimum energy paths for HF formation up on electron capture and the underlying orbital structure of the respective molecular anions. We show that perfluorination of the aromatic ring in these compounds plays an important role in enabling HF formation by further lowering the threshold for this process and through favorable influence on the orbital structure, such that DEA is promoted. We argue that this approach may offer a path for tailoring new and efficient radiosensitizers.


Assuntos
Gases/química , Fenóis/química , Radiossensibilizantes/química , Elétrons , Halogenação , Modelos Moleculares , Termodinâmica
20.
J Am Chem Soc ; 144(6): 2455-2459, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35118859

RESUMO

Exploring materials that can absorb near-infrared (NIR) light to produce reactive oxygen species (ROS) is necessary for many fields. Herein we show that thulium oxide nanoparticles are viable for NIR-stimulated ROS generation. This property may be related to the unique energy levels, large absorption cross section, low fluorescence emission, and ∼10-3 s lifetime of the 3H4 state of Tm ions. We further demonstrate the impact of these nanoparticles on photodynamic therapy (PDT), in which impressive tumor inhibition was recorded after exposure to either a broadband halogen lamp or an 808 nm laser. Our results may provide insight into the areas of photocatalysis, pollution treatment, and fine chemical synthesis.


Assuntos
Nanopartículas Metálicas/uso terapêutico , Neoplasias/tratamento farmacológico , Radiossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/química , Túlio/uso terapêutico , Animais , Linhagem Celular Tumoral , Feminino , Raios Infravermelhos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Camundongos Endogâmicos BALB C , Camundongos Nus , Fotoquimioterapia , Radiossensibilizantes/química , Radiossensibilizantes/efeitos da radiação , Túlio/química , Túlio/efeitos da radiação
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