Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer.

Engineered nanomaterials that produce reactive oxygen species on exposure to X- and gamma-rays used in radiation therapy offer promise of novel cancer treatment strategies. Similar to photodynamic therapy but suitable for large and deep tumors, this new approach where nanomaterials acting as sensitizing agents are combined with clinical radiation can be effective at well-tolerated low radiation doses. Suitably engineered nanomaterials can enhance cancer radiotherapy by increasing the tumor selectivity and decreasing side effects. Additionally, the nanomaterial platform offers therapeutically valuable functionalities, including molecular targeting, drug/gene delivery, and adaptive responses to trigger drug release. The potential of such nanomaterials to be combined with radiotherapy is widely recognized. In order for further breakthroughs to be made, and to facilitate clinical translation, the applicable principles and fundamentals should be articulated. This review focuses on mechanisms underpinning rational nanomaterial design to enhance radiation therapy, the understanding of which will enable novel ways to optimize its therapeutic efficacy. A roadmap for designing nanomaterials with optimized anticancer performance is also shown and the potential clinical significance and future translation are discussed

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Abstract. Radiation-induced bystander effects occur in cells that are not directly irradiated but that communicate with irradiated cells via secreted into culture medium soluble factors or gap junction. This effect induces in irradiated and neighboring cells persistent long-term changes that result in delayed death or genomic instability leading to neoplastic transformation. Non-irradiated human normal lymphocytes were incubated in a medium transferred from irradiated another samples of lymphocytes (ICM -irradiation-conditioned medium). Immediately after replacement of the normal or conditioned medium antioxidant vitamins C or E were added. In lymphocytes incubated in a normal medium (control) or conditioned medium, with or without vitamins, the chromosomal damage and apoptosis were estimated. The results show that medium from irradiated cells (ICM) induces in normal lymphocytes micronuclei and condensation of chromatin characteristic of processes of apoptosis. Conditioned medium did not influence cell cycle division. Bystander effect-induced formation of micronuclei was inhibited by antioxidant vitamins C and E, but this had no effect on the induction of apoptosis. These observations suggest that antioxidant vitamins are able to modify radiation-induced bystander effect (by preventing the increase in micronuclei), without inhibiting elimination of damaged cells via apoptosis. This finding could have significant implication for estimating risks of radiation exposure

Medium-mediated bystander response of X-ray-irradiated normal human lymphocytes in vitro

Radiation-induced bystander effects occur in cells that are not directly irradiated but that communicate with irradiated cells via secreted into culture medium soluble factors or gap junction. This effect induces in irradiated and neighboring cells persistent long-term changes that result in delayed death or genomic instability leading to neoplastic transformation. Non-irradiated human normal lymphocytes were incubated in a medium transferred from irradiated another samples of lymphocytes (ICM - irradiation-conditioned medium). Immediately after replacement of the normal or conditioned medium antioxidant vitamins C or E were added. In lymphocytes incubated in a normal medium (control) or conditioned medium, with or without vitamins, the chromosomal damage and apoptosis were estimated. The results show that medium from irradiated cells (ICM) induces in normal lymphocytes micronuclei and condensation of chromatin characteristic of processes of apoptosis. Conditioned medium did not influence cell cycle division. Bystander effect-induced formation of micronuclei was inhibited by antioxidant vitamins C and E, but this had no effect on the induction of apoptosis. These observations suggest that antioxidant vitamins are able to modify radiation-induced bystander effect (by preventing the increase in micronuclei), without inhibiting elimination of damaged cells via apoptosis. This finding could have significant implication for estimating risks of radiation exposure

Clastogenic effects in human lymphocytes exposed to low and high dose rate X-ray irradiation and vitamin C

In the present work we investigated the ability of vitamin C to modulate clastogenic effects induced in cultured human lymphocytes by X-irradiation delivered at either high (1 Gy/min) or low dose rate (0.24 Gy/min). Biological effects of the irradiation were estimated by cytokinesis-block micronucleus assay including the analysis of the frequency of micronuclei (MN) and apoptotic cells as well as calculation of nuclear division index (NDI). The numbers of micronucleated binucleate lymphocytes (MNCBL) were 24.85 š 2.67% and 32.56 š 3.17% in cultures exposed to X-rays (2 Gy) delivered at low and high dose rates, respectively. Addition of vitamin C (1-20 mi g/ml) to the medium of cultures irradiated with the low dose rate reduced the frequency of micronucleated lymphocytes with multiple MN in a concentration-dependent manner. Lymphocytes exposed to the high dose rate radiation showed a U-shape response: low concentration of vitamin C significantly reduced the number of MN, whereas high concentration influenced the radiation-induced total number of micronucleated cells insignificantly, although it increased the number of cells with multiple MN. Addition of vitamin C significantly reduced the fraction of apoptotic cells, irrespective of the X-ray dose rate. These results indicate that radiation dose rate is an important exposure factor, not only in terms of biological cell response to irradiation, but also with respect to the modulating effects of antioxidants

The quantitative and qualitative changes of sugars in sour cherry fruit subjected to osmo-convective drying

Analizowano zmiany zawartości składników cukrowych w trakcie odwadniania osmotycznego wiśni w celu określenia proporcji między zawartością cukrów w produkcie końcowym a ilością cukrów pochodzących naturalnie z surowca. Owoce ośmiu odmian wiśni poddawano odwadnianiu osmotycznemu w 60-procentowym roztworze sacharozy i suszono konwekcyjnie. Analizę ilościową i jakościową cukrów wykonano metodą HPLC w surowcu mrożonym, odwodnionym oraz w suszu. Dominującymi cukrami w surowcu była glukoza (46–61%) i fruktoza (34–39%). Wiśnie zawierały też 12–20% sorbitolu. Proces odwadniania spowodował przyrosty fruktozy oraz spadki zawartości sorbitolu; zmiany zawartości glukozy nie były jednoznaczne. W sezonie 2009 w owocach odwadnianych stwierdzono obecność 2–20 g·100 g–1 s.s. sacharozy, która podczas suszenia konwekcyjnego w całości uległa hydrolizie. Zmiany pozostałych składników na etapie suszenia były relatywnie niewielkie. W ogólnym ilościowym bilansie składników cukrowych stwierdzono zaledwie 11-procentowy wzrost ich zawartości w suszu w stosunku do surowca, wykazano natomiast znaczące zmiany składu jakościowego. Z surowca tracony był sorbitol na rzecz znacznego wzrostu zawartości fruktozy.Osmotic treatment of plant tissue prior to drying results in a water content reduction that shortens drying time. Simultaneously, the infused osmotic agent modifi es the taste profi le of the treated tissue. In the case of sour cherries, osmotic dehydration causes an improvement in sensory characteristics, which enables direct consumption of dried product. Among different osmotic agents, sucrose has shown to be one of the most popular, as not only does it display the above characteristic, but additionally has been found to have a protective effect on bioactive compound retention. Unfortunately, recent literature seams to focus on the negative connection between high sugar consumption and the development of chronic diseases. In respect of this, trials have been undertaken to ascertain the precise qualitative and quantitative changes in sugar components provoked by osmotic dehydration in sour cherry tissue during osmo-dried fruit production. Additionally, the proportion between added and native sugar content was calculated. Fruits of 8 cultivars of sour cherries collected in 2009 and 2010 seasons were subjected to osmotic treatment (60° Brix sucrose solution, 1 hour at 40°C) and then convectively dried for 8 hours (3 m·s–1, 60°C). At each stage of processing (raw material, osmo-treated fruit, dried fruit) the precise analyses of sucrose, glucose, fructose and sorbitol contents were carried with using the HPLC method. Experiments were performed in two technological repetitions for both seasons. Irrespectively of cultivar and season glucose was quantifi ed as the predominant sugar component accounting for 46–61%. The second abundant was fructose ranging between 34–39%. The sour cherry fruit contained also substantial amount of sorbitol (12–20%). As it was expected, the applied osmotic dehydration treatment led to signifi cant changes in sugar components pattern. During 1 hour process the fructose contents increased (13–91%), which was associated with simultaneous sorbitol losses (64–85%). At this stage the signifi cant decrease of glucose/fructose ratio was observed. Further convective drying stage hardly affected sugar component composition, excluding losses of small sucrose amounts found in the osmo-treated samples form 2009 season trials. Although 60° Brix sucrose solution was used as the osmotic agent for pre-drying treatment, no sucrose in the fi nal dried fruit products were found. From the results of the experiments undertaken it can be confi rmed that on average, only 11% more sugar was present in dried product than in the raw material form. What must be noted, however, are the substantial changes in singular sugar constituents proportions, especially when it is considered from the dietetic point of view. Irrespectively of season and cultivar investigated, during the process, the sorbitol (known for its reduced caloric content and laxative properties) was drastically lowered, while the fructose amount signifi cantly increased