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Anti-cancer activity of ZnO chips by sustained zinc ion release.

ABSTRACT: We report anti-cancer activity of ZnO thin-film-coated chips by sustained release of zinc ions. ZnO chips were fabricated by precisely tuning ZnO thickness using atomic layer deposition, and their potential to release zinc ions relative to the number of deposition cycles was evaluated. ZnO chips exhibited selective cytotoxicity in human B lymphocyte Raji cells while having no effect on human peripheral blood mononuclear cells. Of importance, the half-maximal inhibitory concentration of the ZnO chip on the viability of Raji cells was 121.5 cycles, which was comparable to 65.7 nM of daunorubicin, an anti-cancer drug for leukemia. Molecular analysis of cells treated with ZnO chips revealed that zinc ions released from the chips increased cellular levels of reactive oxygen species, including hydrogen peroxide, which led to the down-regulation of anti-apoptotic molecules (such as HIF-1α, survivin, cIAP-2, claspin, p-53, and XIAP) and caspase-dependent apoptosis. Because the anti-cancer activity of ZnO chips and the mode of action were comparable to those of daunorubicin, the development and optimization of ZnO chips that gradually release zinc ions might have clinical anti-cancer potential. A further understanding of the biological action of ZnO-related products is crucial for designing safe biomaterials with applications in disease treatment.

SUBMITTER: Moon SH

PROVIDER: S-EPMC5615914 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Anti-cancer activity of ZnO chips by sustained zinc ion release.

Moon Seong-Hee SH Choi Won Jin WJ Choi Sik-Won SW Kim Eun Hye EH Kim Jiyeon J Lee Jeong-O JO Kim Seong Hwan SH

Toxicology reports 20160319

We report anti-cancer activity of ZnO thin-film-coated chips by sustained release of zinc ions. ZnO chips were fabricated by precisely tuning ZnO thickness using atomic layer deposition, and their potential to release zinc ions relative to the number of deposition cycles was evaluated. ZnO chips exhibited selective cytotoxicity in human B lymphocyte Raji cells while having no effect on human peripheral blood mononuclear cells. Of importance, the half-maximal inhibitory concentration of the ZnO c ...[more]

PMID: 28959565

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Project description:Post-operative abdominal adhesions are the leading cause of bowel obstruction and a major cause of chronic pain and infertility. Further, adhesion formation complicates any re-operative strategy, increasing the length of surgery and rendering a safe minimally invasive approach impossible. Despite the prevalence of abdominal adhesions, which form following 50-90% of abdominal operations, no proven preventative or treatment strategy has been developed. Our group previously established a mouse model to study adhesive disease in vivo and explored adhesion biology across mouse and human tissues. We established that adhesions derive primarily from the visceral peritoneum, are composed of poly-clonally proliferating tissue-resident fibroblasts, and identified that modulation of JUN signaling regulates abdominal adhesiogenesis following surgery. We identified a small molecule JUN inhibitor (T-5224) that decreases adhesion formation. Here, we encapsulated T-5224 in a shear-thinning hydrogel with anti-adhesion properties for intra-peritoneal delivery and sustained-release for post-operative adhesion prevention. We extensively characterized this novel therapeutic system, and found it to be safe, systemically well-tolerated, and efficacious in reducing adhesions in our mouse model. Furthermore, this therapeutic system minimizes not only the quantity of adhesions that form, but also limits the maturation of adhesion fibrosis at an ultrastructural level. Critical towards clinical translation, we developed a large mammal (porcine) preclinical model of adhesions with bowel resection and showed that the T-5224-hydrogel therapeutic provides robust adhesion prevention without deleterious effects on bowel anastomosis or abdominal wall (laparotomy) wound healing. At a single-cell transcriptomic level, treated fibroblasts in our pig model show decreased JUN and associated pathway signaling. Adhesion biology shares close similarities across surgical sites (e.g. thoracic, joint space, neurological); as such, this formulation has significant potential for applicability across the body. Material properties of the T-5224-hydrogel formulation, such as shear-thinning and self-healing, also facilitate ease of open or minimally invasive application. Therefore, these results are promising for immediate and high-impact translation to patient care to address a common, unmet clinical need.

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Anti-cancer activity of ZnO chips by sustained zinc ion release.

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Anti-cancer activity of ZnO chips by sustained zinc ion release.

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