Zinc oxide (ZnO) nanoparticles absorb UV light efficiently while remaining transparent in the visible light spectrum rendering them attractive in cosmetics and polymer films. Their broad use, however, raises concerns regarding potential environmental health risks and it has been shown that ZnO nanoparticles can induce significant DNA damage and cytotoxicity. Even though research on ZnO nanoparticle synthesis has made great progress, efforts on developing safer ZnO nanoparticles that maintain their inherent optoelectronic properties while exhibiting minimal toxicity are limited. Here, a safer-by-design concept was pursued by hermetically encapsulating ZnO nanorods in a biologically inert, nanothin amorphous SiO2 coating during their gas-phase synthesis. It is demonstrated that the SiO2 nanothin layer hermetically encapsulates the core ZnO nanorods without altering their optoelectronic properties. Furthermore, the effect of SiO2 on the toxicological profile of the core ZnO nanorods was assessed using the Nano-Cometchip assay by monitoring DNA damage at a cellular level using human lymphoblastoid cells (TK6). Results indicate significantly lower DNA damage (>3 times) for the SiO2-coated ZnO nanorods compared to uncoated ones. Such an industry-relevant, scalable, safer-by-design formulation of nanostructured materials can liberate their employment in nano-enabled products and minimize risks to the environment and human health.

BackgroundNanoparticle pharmacokinetics and biological effects are influenced by several factors. We assessed the effects of amorphous SiO2 coating on the pharmacokinetics of zinc oxide nanoparticles (ZnO NPs) following intratracheal (IT) instillation and gavage in rats.MethodsUncoated and SiO2-coated ZnO NPs were neutron-activated and IT-instilled at 1 mg/kg or gavaged at 5 mg/kg. Rats were followed over 28 days post-IT, and over 7 days post-gavage. Tissue samples were analyzed for 65Zn radioactivity. Pulmonary responses to instilled NPs were also evaluated at 24 hours.ResultsSiO2-coated ZnO elicited significantly higher inflammatory responses than uncoated NPs. Pulmonary clearance of both 65ZnO NPs was biphasic with a rapid initial t1/2 (0.2 - 0.3 hours), and a slower terminal t1/2 of 1.2 days (SiO2-coated ZnO) and 1.7 days (ZnO). Both NPs were almost completely cleared by day 7 (>98%). With IT-instilled 65ZnO NPs, significantly more 65Zn was found in skeletal muscle, liver, skin, kidneys, cecum and blood on day 2 in uncoated than SiO2-coated NPs. By 28 days, extrapulmonary levels of 65Zn from both NPs significantly decreased. However, 65Zn levels in skeletal muscle, skin and blood remained higher from uncoated NPs. Interestingly, 65Zn levels in bone marrow and thoracic lymph nodes were higher from coated 65ZnO NPs. More 65Zn was excreted in the urine from rats instilled with SiO2-coated 65ZnO NPs. After 7 days post-gavage, only 7.4% (uncoated) and 6.7% (coated) of 65Zn dose were measured in all tissues combined. As with instilled NPs, after gavage significantly more 65Zn was measured in skeletal muscle from uncoated NPs and less in thoracic lymph nodes. More 65Zn was excreted in the urine and feces with coated than uncoated 65ZnO NPs. However, over 95% of the total dose of both NPs was eliminated in the feces by day 7.ConclusionsAlthough SiO2-coated ZnO NPs were more inflammogenic, the overall lung clearance rate was not affected. However, SiO2 coating altered the tissue distribution of 65Zn in some extrapulmonary tissues. For both IT instillation and gavage administration, SiO2 coating enhanced transport of 65Zn to thoracic lymph nodes and decreased transport to the skeletal muscle.

Nanoparticle (NP) pharmacokinetics and biological effects are influenced by many factors, especially surface physicochemical properties. We assessed the effects of an amorphous silica coating on the fate of zinc after intravenous (IV) injection of neutron activated uncoated 65ZnO or silica-coated 65ZnO NPs in male Wistar Han rats. Groups of IV-injected rats were sequentially euthanized, and 18 tissues were collected and analyzed for 65Zn radioactivity. The protein coronas on each ZnO NP after incubation in rat plasma were analyzed by SDS-PAGE gel electrophoresis and mass spectrometry of selected gel bands. Plasma clearance for both NPs was biphasic with rapid initial and slower terminal clearance rates. Half-lives of plasma clearance of silica-coated 65ZnO were shorter (initial - <1 minute; terminal - 2.5 minutes) than uncoated 65ZnO (initial - 1.9 minutes; terminal - 38 minutes). Interestingly, the silica-coated 65ZnO group had higher 65Zn associated with red blood cells and higher initial uptake in the liver. The 65Zn concentrations in all the other tissues were significantly lower in the silica-coated than uncoated groups. We also found that the protein corona formed on silica-coated ZnO NPs had higher amounts of plasma proteins, particularly albumin, transferrin, A1 inhibitor 3, α-2-hs-glycoprotein, apoprotein E, and α-1 antitrypsin. Surface modification with amorphous silica alters the protein corona, agglomerate size, and zeta potential of ZnO NPs, which in turn influences ZnO biokinetic behavior in the circulation. This emphasizes the critical role of the protein corona in the biokinetics, toxicology, and nanomedical applications of nanoparticles.

Background Zinc oxide engineered nanoparticles (ZnO ENPs) have potential as nanomedicines due to their inherent properties. Studies have described their pulmonary impact, but less is known about the consequences of ZnO ENP interactions with the liver. This study was designed to describe the effects of ZnO ENPs on the liver and Kupffer cells after intravenous (IV) administration. Materials and methods First, pharmacokinetic studies were conducted to determine the tissue distribution of neutron-activated 65 ZnO ENPs post-IV injection in Wistar Han rats. Then, a noninvasive in vivo method to assess Kupffer cell phagosomal motility was employed using ferromagnetic iron particles and magnetometry. We also examined whether prior IV injection of ZnO ENPs altered Kupffer cell bactericidal activity on circulating Pseudomonas aeruginosa . Serum and liver tissues were collected to assess liver-injury biomarkers and histological changes, respectively. Results We found that the liver was the major site of initial uptake of 65 ZnO ENPs. There was a time-dependent decrease in tissue levels of 65 Zn in all organs examined, refecting particle dissolution. In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility. Animals challenged with P . aeruginosa 24 hours post-ZnO ENP injection showed an initial (30 minutes) delay in vascular bacterial clearance. However, by 4 hours, IV-injected bacteria were cleared from the blood, liver, spleen, lungs, and kidneys. Seven days post-ZnO ENP injection, creatine phosphokinase and aspartate aminotransferase levels in serum were significantly increased. Histological evidence of hepatocyte damage and marginated neutrophils were observed in the liver. Conclusion Administration of ZnO ENPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury, but did not alter bacterial clearance from the blood or killing in the liver, spleen, lungs, or kidneys. Our data show that diminished Kupffer cell organelle motion correlated with ZnO ENP-induced liver injury.

Laparoscopic morcellation is a technique used in gynecological surgeries such as hysterectomy and myomectomy to remove uteri and uterine fibroids (leiomyomas) through a small abdominal incision. Current morcellators use blades or bipolar energy to cut tissue into small pieces that are then removed through laparoscopic ports in a piecewise manner. These existing approaches have several limitations; (1) they are time consuming as the tissue must be manually moved over the devices during the cutting step and removal is piecewise, (2) they can lead to accidental damage to surrounding healthy tissue inside the body and (3) they do not provide safe containment of tissue during the morcellation process which can lead to seeding (spreading and regrowth) of benign or potentially cancerous tissue. This paper describes a laparoscopic morcellator that overcomes these limitations through a new design that is based on an enclosed, motor-actuated mesh that applies only an inward-directed cutting force to the tissue after it has been loaded into the protective mesh and bag. The deterministic design approach that led to this concept is presented along with the detailed electromechanical design. The prototype is tested on soft vegetables and an animal model to demonstrate successful morcellation and how the device would be compatible with current clinical practice. Results show that the time required to morcellate with the new device for a set of tests on animal tissue is relatively uniform across samples with widely varying parameters. Including tissue manipulation and extraction time, the new device is shown to have an improvement in terms of speed over current morcellators. The mean time for cutting animal tissue ranging from 100 g to 360 g was 30 s with small variations due to initial conditions. The time for cutting is expected to remain approximately constant as tissue size increases. There is also minimal risk of the protective bag ripping due to the inward-cutting action of the mesh, thereby potentially significantly reducing the risk of seeding during clinical procedures; thus, further increasing patient safety. Finally, this design may be applicable to other procedures involving removal of tissue in nongynecologic surgeries, such as full or partial kidney or spleen removal.

INTRODUCTION: Although women who have sex with women are at risk for cervical cancer, they exhibit poor Pap screening practices. Commonly reported barriers to care include a low perceived cervical cancer risk, experiences of homophobia, or lack of insurance. Relationships between women who have sex with men and their health care providers might further discourage patients to seek care. It was the objective of this study to 1) evaluate patterns of cervical cancer screening among women who have sex with women; 2) investigate perceptions of their health care providers; and 3) assess the perceived need for education related to this topic.METHODS: Participants were recruited from Los Angeles women who have sex with women centers and received a validated questionnaire. The sample included 33 predominately Hispanic women who have sex with women. Data were analyzed using REDCap.RESULTS: A total of 75.8% of women experienced regular Pap screenings every 1-3 years. The minority of women who have sex with women experienced educational interventions regarding cervical cancer by their health care provider. Most women who have sex with women stated health care providers should be more aware of the needs of women who have sex with women; they did not feel ashamed to disclose their sexual orientation. Most participants reported practicing "protected sex," yet 60% never used protection. Sixty-seven percent perceived themselves as having a low risk to develop cervical cancer. CONCLUSION:The majority of participants complied with recommended Pap screening guidelines. Our participants would like their health care provider to be more aware of women who have sex with women patients' health needs. Health care providers have to be informed and provide tailored care and sensitive patient education on topics such as safe sex practices. Understanding our women who have sex with women patients will translate into better health care delivery to this demographic and minimize apparent health care disparities.