Zinc oxide nanoparticle (ZnO NP)-based sunscreens are generally considered safe because the ZnO NPs do not penetrate through the outermost layer of the skin, the stratum corneum (SC). However, cytotoxicity of zinc ions in the viable epidermis (VE) after dissolution from ZnO NP and penetration into the VE is ill-defined. We therefore quantified the relative concentrations of endogenous and exogenous Zn using a rare stable zinc-67 isotope (⁶⁷Zn) ZnO NP sunscreen applied to excised human skin and the cytotoxicity of human keratinocytes (HaCaT) using multiphoton microscopy, zinc-selective fluorescent sensing, and a laser-ablation inductively coupled plasma–mass spectrometry (LA-ICP-MS) methodology. Multiphoton microscopy with second harmonic generation imaging showed that ⁶⁷ZnO NPs were retained on the surface or within the superficial layers of the SC. Zn fluorescence sensing revealed higher levels of labile and intracellular zinc in both the SC and VE relative to untreated skin, confirming that dissolved zinc species permeated across the SC into the VE as ionic Zn and significantly not as ZnO NPs. Importantly, the LA-ICP-MS estimated exogenous ⁶⁷Zn concentrations in the VE of 1.0 ± 0.3 μg/mL are much lower than that estimated for endogenous VE zinc of 4.3 ± 0.7 μg/mL. Furthermore, their combined total zinc concentrations in the VE are much lower than the exogenous zinc concentration of 21 to 31 μg/mL causing VE cytotoxicity, as defined by the half-maximal inhibitory concentration of exogenous ⁶⁷Zn found in human keratinocytes (HaCaT). This speaks strongly for the safety of ZnO NP sunscreens applied to intact human skin and the associated recent US FDA guidance.

Nanodiamonds were coated in lectins to target glycan receptors on astrocytes, neurons and microglia. The uptake in each cell type was variable depending on their coating of Aleuria aurantia lectin, wheat germ agglutinin or tomato lectin.

Applications of nanoparticles (NPs) in the life sciences require control over their properties in protein-rich biological fluids, as an NP quickly acquires a layer of proteins on the surface, forming the so-called “protein corona” (PC). Understanding the composition and kinetics of the PC at the molecular level is of considerable importance for controlling NP interaction with cells. Here, we present a systematic study of hard PC formation on the surface of upconversion nanoparticles (UCNPs) coated with positively-charged polyethyleneimine (PEI) and negatively-charged poly (acrylic acid) (PAA) polymers in serum-supplemented cell culture medium. The rationale behind the choice of UCNP is two-fold: UCNP represents a convenient model of NP with a size ranging from 5 nm to >200 nm, while the unique photoluminescent properties of UCNP enable direct observation of the PC formation, which may provide new insight into this complex process. The non-linear optical properties of UCNP were utilised for direct observation of PC formation by means of fluorescence correlation spectroscopy. Our findings indicated that the charge of the surface polymer coating was the key factor for the formation of PC on UCNPs, with an ensuing effect on the NP–cell interactions.

There is potential for cannabidiol to act as an analgesic, anxiolytic and antipsychotic active ingredient; however, there is a need to find alternate administration routes to overcome its low oral bioavailability. In this work, we propose a new delivery vehicle based on encapsulation of cannabidiol within organosilica particles as drug delivery vehicles, which are subsequently incorporated within polyvinyl alcohol films. We investigated the long-term stability of the encapsulated cannabidiol, as well as its release rate, in a range of simulated fluids with different characterization techniques, including Fourier Transform Infrared (FT-IR) and High-performance Liquid Chromatography (HPLC). Finally, we determined the transdermal penetration in an ex vivo skin model. Our results show that cannabidiol is stable for up to 14 weeks within polyvinyl alcohol films at a range of temperatures and humidity. Release profiles are first-order, consistent with a mechanism involving diffusion of the cannabidiol (CBD) out of the silica matrix. The silica particles do not penetrate beyond the stratum corneum in the skin. However, cannabidiol penetration is enhanced and is detected in the lower epidermis, which was 0.41% of the total CBD in a PVA formulation compared with 0.27% for pure CBD. This is partly due to an improvement of its solubility profile as it is released from the silica particles, but we cannot rule out effects of the polyvinyl alcohol. Our design opens a route for new membrane technologies for cannabidiol and other cannabinoid products, where administration via non-oral or pulmonary routes can lead to better outcomes for patient cohorts in a range of therapeutics.

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Herein, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model was built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellularized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2–3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development, and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal compartments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diagnosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.

Zinc oxide nanoparticle (ZnO NPs) sunscreens are generally considered safe because the ZnO NP do not penetrate through the outermost stratum corneum (SC) layer of the skin. However, cytotoxicity of zinc ions in the viable epidermis (VE), after release from ZnO NP and penetration into the VE, is ill-defined. We therefore quantified the relative concentrations of endogenous and exogenous Zn using a rare stable zinc-67 isotope (⁶⁷Zn) ZnO NP sunscreen applied to human skin and the cytotoxicity of human keratinocytes (HaCaT) using multiphoton microscopy, zinc-selective fluorescent sensing and laser-ablation inductively-coupled-plasma mass-spectrometry (LA-ICP-MS) methodology. Multi-photon microscopy with second harmonic generation showed that ⁶⁷ZnO NPs were retained on the surface or within the SC. Zn fluorescence sensing revealed higher levels of labile and intracellular zinc in both SC and VE relative to untreated skin, confirming that zinc permeated through the SC into the VE as ionic Zn and not as ZnO NPs. Importantly, the LA-ICP-MS estimated exogenous ⁶⁷Zn concentrations in the VE of 1.0 ± 0.3 mg/mL are much lower than that estimated for endogenous VE zinc of 4.3 ± 0.7 mg/mL. Further, their combined total zinc concentrations in the VE are much less than the exogenous zinc concentration of 21 to 31 mg/mL causing VE cytotoxicity, as defined by the from half maximal inhibitory concentration of exogenous ⁶⁷Zn found in human keratinocytes (HaCaT). This speaks strongly for the safety of ZnO NP sunscreens applied to intact human skin and the associated recent US FDA guidance.