Cold-Responsive Hyaluronated Upconversion Nanoplatform for Transdermal Cryo-Photodynamic Cancer Therapy.

Cryotherapy leverages controlled freezing temperature interventions to engender a cascade of tumor-suppressing effects. However, its bottleneck lies in the standalone ineffectiveness. A promising strategy is using nanoparticle therapeutics to augment the efficacy of cryotherapy. Here, a cold-responsive nanoplatform composed of upconversion nanoparticles coated with silica - chlorin e6 - hyaluronic acid (UCNPs@SiO2-Ce6-HA) is designed. This nanoplatform is employed to integrate cryotherapy with photodynamic therapy (PDT) in order to improve skin cancer treatment efficacy in a synergistic manner. The cryotherapy appeared to enhance the upconversion brightness by suppressing the thermal quenching. The low-temperature treatment afforded a 2.45-fold enhancement in the luminescence of UCNPs and a 3.15-fold increase in the photodynamic efficacy of UCNPs@SiO2-Ce6-HA nanoplatforms. Ex vivo tests with porcine skins and the subsequent validation in mouse tumor tissues revealed the effective HA-mediated transdermal delivery of designed nanoplatforms to deep tumor tissues. After transdermal delivery, in vivo photodynamic therapy using the UCNPs@SiO2-Ce6-HA nanoplatforms resulted in the optimized efficacy of 79% in combination with cryotherapy. These findings underscore the Cryo-PDT as a truly promising integrated treatment paradigm and warrant further exploring the synergistic interplay between cryotherapy and PDT with bright upconversion to unlock their full potential in cancer therapy.

Insights into structural defect formation in individual InP/ZnSe/ZnS quantum dots under UV oxidation.

InP/ZnSe/ZnS quantum dots (QDs) stand as promising candidates for advancing QD-organic light-emitting diodes (QLED), but low emission efficiency due to their susceptibility to oxidation impedes applications. Structural defects play important roles in the emission efficiency degradation of QDs, but the formation mechanism of defects in oxidized QDs has been less investigated. Here, we investigated the impact of diverse structural defects formation on individual QDs and propagation during UV-facilitated oxidation using high-resolution (scanning) transmission electron microscopy. UV-facilitated oxidation of the QDs alters shell morphology by the formation of surface oxides, leaving ZnSe surfaces poorly passivated. Further oxidation leads to the formation of structural defects, such as dislocations, and induces strain at the oxide-QD interfaces, facilitating In diffusion from the QD core. These changes in the QD structures result in emission quenching. This study provides insight into the formation of structural defects through photo-oxidation, and their effects on emission properties of QDs.

Sialylated IVIg promotes clinical improvements in a rabbit dry eye model by regulating inflammatory cytokines.

Dry eye disease (DED) is caused by a loss of homeostasis of the tear film, which results in visual disturbance, ocular surface inflammation and damage, and neurosensory abnormalities. Although it is prevalent in 5-50% of the global population, there are limited clinical options for its treatment. This study explored the potential use of human intravenous immunoglobulin (IVIg) and its enriched fractions of sialylation, sialylated IVIg (sIVIg), as a treatment for DED. Fifteen female New Zealand white rabbits were topically instilled with 0.2% benzalkonium chloride (BAC) twice daily for five consecutive days to induce experimental dry eye. Saline, 0.4% IVIg, or 0.04% sIVIg eye drops were instilled twice daily for 20 consecutive days. Clinical evaluations, such as non-invasive tear break-up time (NIBUT) and corneal fluorescein staining (CFS), were conducted. mRNA levels of mucin 4, mucin 16, TNF-α, IL-1ß, MMP9, IL-10, TGF-ß, and CD209 in rabbit conjunctival tissues were examined using reverse transcription polymerase chain reaction (RT-PCR) or quantitative RT-PCR (qRT-PCR). The relationships between CD209 family members in rabbits and various mammalian species were analyzed using a phylogenetic tree. IVIg or sIVIg treatment resulted in clinical improvements in the rabbit DED model. The inflammatory cytokines, TNF-α and IL-1ß, were increased and mucin 4 and mucin 16, cell surface-associated mucins, were decreased in BAC-induced dry eye. Following IVIg or sIVIg treatment, inflammatory cytokines decreased, whereas the anti-inflammatory cytokine, IL-10, increased substantially. Moreover, a 10-fold lower sIVIg treatment dose resulted in prolonged IL-10 production, representing a significantly improved DED compared to IVIg. Furthermore, the expression of rabbit CD209 mRNA in the rabbit conjunctiva and its close relationship with primate homologs suggest that it may interact with IVIg or sIVIg to promote IL-10 expression, as previously described in humans. At a lower dosage, sIVIg showed a more efficient improvement in DED, making it a promising new candidate medication for DED.

Moisture-Induced Degradation of Quantum-Sized Semiconductor Nanocrystals through Amorphous Intermediates.

Elucidating the water-induced degradation mechanism of quantum-sized semiconductor nanocrystals is an important prerequisite for their practical application because they are vulnerable to moisture compared to their bulk counterparts. In-situ liquid-phase transmission electron microscopy is a desired method for studying nanocrystal degradation, and it has recently gained technical advancement. Herein, the moisture-induced degradation of semiconductor nanocrystals is investigated using graphene double-liquid-layer cells that can control the initiation of reactions. Crystalline and noncrystalline domains of quantum-sized CdS nanorods are clearly distinguished during their decomposition with atomic-scale imaging capability of the developed liquid cells. The results reveal that the decomposition process is mediated by the involvement of the amorphous-phase formation, which is different from conventional nanocrystal etching. The reaction can proceed without the electron beam, suggesting that the amorphous-phase-mediated decomposition is induced by water. Our study discloses unexplored aspects of moisture-induced deformation pathways of semiconductor nanocrystals, involving amorphous intermediates.

Direct Observation of Off-Stoichiometry-Induced Phase Transformation of 2D CdSe Quantum Nanosheets.

Crystal structures determine material properties, suggesting that crystal phase transformations have the potential for application in a variety of systems and devices. Phase transitions are more likely to occur in smaller crystals; however, in quantum-sized semiconductor nanocrystals, the microscopic mechanisms by which phase transitions occur are not well understood. Herein, the phase transformation of 2D CdSe quantum nanosheets caused by off-stoichiometry is revealed, and the progress of the transformation is directly observed by in situ transmission electron microscopy. The initial hexagonal wurtzite-CdSe nanosheets with atomically uniform thickness are transformed into cubic zinc blende-CdSe nanosheets. A combined experimental and theoretical study reveals that electron-beam irradiation can change the stoichiometry of the nanosheets, thereby triggering phase transformation. The loss of Se atoms induces the reconstruction of surface atoms, driving the transformation from wurtzite-CdSe(11 2 ¯ $\bar{2}$ 0) to zinc blende-CdSe(001) 2D nanocrystals. Furthermore, during the phase transformation, unconventional dynamic phenomena occur, including domain separation. This study contributes to the fundamental understanding of the phase transformations in 2D quantum-sized semiconductor nanocrystals.

Real-space imaging of nanoparticle transport and interaction dynamics by graphene liquid cell TEM.

Thermal motion of colloidal nanoparticles and their cohesive interactions are of fundamental importance in nanoscience but are difficult to access quantitatively, primarily due to the lack of the appropriate analytical tools to investigate the dynamics of individual particles at nanoscales. Here, we directly monitor the stochastic thermal motion and coalescence dynamics of gold nanoparticles smaller than 5 nm, using graphene liquid cell (GLC) transmission electron microscopy (TEM). We also present a novel model of nanoparticle dynamics, providing a unified, quantitative explanation of our experimental observations. The nanoparticles in a GLC exhibit non-Gaussian, diffusive motion, signifying dynamic fluctuation of the diffusion coefficient due to the dynamically heterogeneous environment surrounding nanoparticles, including organic ligands on the nanoparticle surface. Our study shows that the dynamics of nanoparticle coalescence is controlled by two elementary processes: diffusion-limited encounter complex formation and the subsequent coalescence of the encounter complex through rotational motion, where surface-passivating ligands play a critical role.

Role of the Precursor Composition in the Synthesis of Metal Ferrite Nanoparticles.

Ternary oxide nanoparticles have attracted much interest because of their intriguing properties, which are not exhibited by binary oxide nanoparticles. However, the synthesis of ternary oxide nanoparticles is not trivial and requires a fundamental understanding of the complicated precursor chemistry that governs the formation mechanism. Herein, we investigate the role of the chemical composition of precursors in the formation of ternary oxide nanoparticles via a combination of mass spectrometry, electron microscopy with elemental mapping, and thermogravimetric analysis. Mn2+, Co2+, and Ni2+ ions easily form bimetallic-oxo clusters with Fe3+ ions with a composition of MFe2O(oleate)6 (M = Mn, Co, Ni). The use of clusters as precursors leads to the successful synthesis of monodisperse metal ferrite nanoparticles (MFe2O4). On the contrary, zinc- or copper-containing complexes are formed independently from iron-oxo clusters in the precursor synthesis. The mixture of complexes without a bimetallic-oxo core yields a mixture of two different nanoparticles. This study reveals the importance of the precursor composition in the synthesis of ternary oxide nanoparticles.