X-Ray responsive nanoparticles with triggered release of nitrite, a precursor of reactive nitrogen species, for enhanced cancer radiosensitization

Nanoscale ◽  
2017 ◽  
Vol 9 (38) ◽  
pp. 14627-14634 ◽  
Author(s):  
Fang Liu ◽  
Junzhe Lou ◽  
Dimitre Hristov

New strategy to enhance cancer radiotherapy: A novel gold nanosystem with surface-grafted nitroimidazole and cell nucleus-targeting peptide achieves the release of a RNS precursor, nitrite, by ionizing radiation. In vitro radiotherapy shows enhanced sensitivity of hypoxic cancer cells to X-ray radiation, presumably due to the generation of both reactive oxygen and nitrogen species.

2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.


2004 ◽  
Vol 172 (4 Part 1) ◽  
pp. 1474-1479 ◽  
Author(s):  
YOICHI MIZUTANI ◽  
HIROYUKI NAKANISHI ◽  
YONG NAN LI ◽  
NODOKA SATO ◽  
AKIHIRO KAWAUCHI ◽  
...  

2007 ◽  
Vol 55 (15) ◽  
pp. 6000-6006 ◽  
Author(s):  
Guan-Jhong Huang ◽  
Ming-Jyh Sheu ◽  
Hsien-Jung Chen ◽  
Yuan-Shiun Chang ◽  
Yaw-Huei Lin

2012 ◽  
Vol 65 (12) ◽  
pp. 1625 ◽  
Author(s):  
Vasilis I. Balas ◽  
Christina N. Banti ◽  
Nikolaos Kourkoumelis ◽  
Sotiris K. Hadjikakou ◽  
George D. Geromichalos ◽  
...  

Crystals of Ph3SnCl (1) were grown from a methanol/acetonitrile solution. Compounds [Ph3SnOH]n (2) and [(Ph2Sn)4Cl2O2(OH)2] (3) were crystallized from diethyl ether/methanol/acetonitrile and hot acetone/water solutions respectively, of the white precipitation, formed by adding KOH to solutions of 1 and [Ph2SnCl2] in 1 : 1 and 1 : 2 molar ratios respectively. Complex 1 was characterized by X-ray crystallography. X-ray structure determination of compounds 2 and 3 confirmed the previously reported identities. The molecular structure of 1, reported here, is a new polymorphic form of the known one for Ph3SnCl. Four independent [Ph3SnCl] molecules constitute the crystal structure of 1. The moieties are packed in two pairs in a tail-to-tail arrangement. Complexes 1–3 were evaluated for their in vitro cytotoxic activity (cell viability) against human cancer cell lines: HeLa (human cervical), MCF-7 (breast, estrogen receptor (ER) positive), MDA-MB-231 (breast, ER negative), A549 (lung), Caki-1 (kidney carcinoma), 786-O (renal adenocarcinoma), K1 (thyroid carcinoma), and the normal human lung cell line MRC-5 (normal human fetal lung fibroblast cells) versus, the normal immortalized human mammary gland epithelial cell line MTSV17 with a sulforhodamine B (SRB) assay. The results show potent cytotoxic activity of the complexes against all cell lines used, which was superior to that of cisplatin (CDDP). Compounds 1–3 showed higher activity against breast cancer cells MCF-7 (ER positive) than against of MDA-MB-231 (ER negative). These findings prompted us to search for possible interaction of these complexes with other cellular elements of fundamental importance in cell proliferation. The influence of these complexes 1–3 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX), as well as their binding affinity towards calf thymus-DNA, were kinetically and theoretically studied.


1999 ◽  
Vol 103 (11) ◽  
pp. 1547-1560 ◽  
Author(s):  
Eugene A. Podrez ◽  
David Schmitt ◽  
Henry F. Hoff ◽  
Stanley L. Hazen

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1687
Author(s):  
Giuliana Bruno ◽  
Sebastian Wenske ◽  
Jan-Wilm Lackmann ◽  
Michael Lalk ◽  
Thomas von Woedtke ◽  
...  

Cold physical plasmas modulate cellular redox signaling processes, leading to the evolution of a number of clinical applications in recent years. They are a source of small reactive species, including reactive nitrogen species (RNS). Wound healing is a major application and, as its physiology involves RNS signaling, a correlation between clinical effectiveness and the activity of plasma-derived RNS seems evident. To investigate the type and reactivity of plasma-derived RNS in aqueous systems, a model with tyrosine as a tracer was utilized. By high-resolution mass spectrometry, 26 different tyrosine derivatives including the physiologic nitrotyrosine were identified. The product pattern was distinctive in terms of plasma parameters, especially gas phase composition. By scavenger experiments and isotopic labelling, gaseous nitric dioxide radicals and liquid phase peroxynitrite ions were determined as dominant RNS. The presence of water molecules in the active plasma favored the generation of peroxynitrite. A pilot study, identifying RNS driven post-translational modifications of proteins in healing human wounds after the treatment with cold plasma (kINPen), demonstrated the presence of in vitro determined chemical pathways. The plasma-driven nitration and nitrosylation of tyrosine allows the conclusion that covalent modification of biomolecules by RNS contributes to the clinically observed impact of cold plasmas.


2020 ◽  
Vol 15 (6) ◽  
pp. 1934578X2093203 ◽  
Author(s):  
Olesya S. Malyarenko ◽  
Lyudmila A. Ivanushko ◽  
Elena L. Chaikina ◽  
Mikhail I. Kusaykin ◽  
Alexandra S. Silchenko ◽  
...  

Radiation therapy is one of the most important approaches to cancer therapy, but radiotoxicity to normal tissue is a serious limitation of this treatment. Compounds which are able to either sensitize cancer cells or protect normal cells to radiation are of great interest. The cytotoxicity of holotoxin A1 and the effects of radiation against DLD-1 and HT-29 cells were measured by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. The effect of the combination of holotoxin A1 with X-ray on colony formation of cancer cells was determined by the soft agar assay. The effect of holotoxin A1 on the recovery of peripheral blood leukocyte number, mass, and cellularity of the lymphoid organs of irradiated mice, as well as on growth of murine Ehrlich solid carcinoma was studied. Holotoxin A1 enhanced the sensitivity of colorectal carcinoma cells to radiation in vitro. Injection of holotoxin A1 to mice led to an increase in the spleen endogenous colony number and peripheral blood leukocyte number, as well as the weight and cellularity of the lymphoid organs of the irradiated mice. Holotoxin A1 in combination with X-ray radiation effectively inhibited the growth of Ehrlich solid carcinoma in vivo. Holotoxin A1 is suggested to be a promising agent for improving the efficiency of radiotherapy.


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