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Chemodynamic therapy (CDT) generating hydroxyl radicals (•OH) by utilizing metal ions reacting with hydrogen peroxide (H2O2) is a highly encouraging strategy for cancer treatment. However, highly expressed GSH in tumor cells severely limits the efficacy of CDT, and CDT alone is also not sufficient to produce excellent antitumor efficiency. Herein, a dual GSH depletion nanosystem (MnO2@PDA@PEG@DOX) was designed and synthesized to achieve synergistic cancer treatment under ultrasound (US) irritation. To achieve an acidic response, dopamine (DA) was loaded onto manganese dioxide, and the water solubility and stability were greatly improved after PEG modification; finally, the loading of doxorubicin (DOX) achieved the combinational therapy. When the nanoparticles arrived at the tumor site, the acidic and high expression of GSH in the tumor microenvironment prompted the degrading of the nanosystem, followed by the release of MnO2 and DOX. The released MnO2 can react with intracellular GSH to produce Mn2+, which realizes chemodynamic therapy by catalyzing H2O2 to generate highly toxic hydroxyl radicals (•OH) at the tumor site; also, the depletion of GSH will significantly promote the level of •OH, improving the efficiency of CDT simultaneously. Moreover, the release of DOX could be boosted by US irradiation, thus enhancing the effect of chemotherapy on DOX and achieving sonodynamic therapy (SDT). Therefore, strategies to enhance CDT efficiency by dual GSH depletion and combining chemotherapy and sonodynamic therapy modalities can provide more ideas and approaches for combination therapy in cancer treatment. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by chronic, progressive scarring of the lung parenchyma, leading to an irreversible decline in lung function. Apart from supportive care, there is currently no specific treatment available to reverse the disease. Based on the fact that tanshinone IIA (TAN) had an effect on protecting against TGF-β1-induced fibrosis through the inhibition of Smad and non-Smad signal pathways to avoid myofibroblasts activation, this study reported the development of the inhalable tanshinone IIA-loaded chitosan-oligosaccharides-coated poly(lactic- co -glycolic acid) (PLGA) nanoparticles (CPN@TAN) for enhancing the pulmonary delivery of tanshinone IIA to treat pulmonary fibrosis. The CPN@TAN with a size of 206.5 nm exhibited excellent in vitro aerosol delivery characteristics, featuring a mass median aerodynamic diameter (MMAD) of 3.967 ± 0.025 μm and a fine particle fraction (FPF) of 70.516 ± 0.929%. Moreover, the nanoparticles showed good stability during atomization and enhanced the mucosal penetration capabilities. The results of confocal spectroscopy confirmed the potential of the nanoparticles as carriers that facilitated the uptake of drugs by NIH3T3, A549, and MH-S cells. Additionally, the nanoparticles demonstrated good in vitro biocompatibility. In a mouse model of bleomycin-induced pulmonary fibrosis, noninvasive inhalation of aerosol CPN@TAN greatly suppressed collagen formation and facilitated re-epithelialization of the destroyed alveolar epithelium without causing systemic toxicity compared with intravenous administration. Consequently, our noninvasive inhalation drug delivery technology based on polymers may represent a promising paradigm and open the door to overcoming the difficulties associated with managing pulmonary fibrosis.

Although targeted therapy has revolutionized oncotherapy, engineering a versatile oncotherapy nanoplatform integrating both diagnostics and therapeutics has always been an intractable challenge to overcome the limitations of monotherapy. Herein, a theranostics platform based on DI/MP-MB has successfully realized the fluorescence detection of disease marker miR-21 and the gene/photothermal/chemo triple synergetic cancer therapy, which can trace the tumor through photothermal and fluorescence dual-mode imaging and overcome the limitations of monotherapy to improve the treatment efficiency of tumors. DI/MP-MB was prepared by magnetic mesoporous silicon nanoparticles (M-MSNs) loaded with doxorubicin (Dox) and new indocyanine green (IR820), and subsequently coating polydopamine as a "gatekeeper", followed by the surface adsorbed with molecular beacons capable of targeting miR-21 for responsive imaging. Under the action of enhanced permeability retention and external magnetic field, DI/MP-MB were targeted and selectively accumulated in the tumor. MiR-21 MB hybridized with miR-21 to form a double strand, which led to the desorption of miR-21 MB from the polydopamine surface and the fluorescence recovery to realize gene silencing and fluorescence imaging for tracking the treatment process. Meanwhile, with the response to the near-infrared irradiation and the tumor's microacid environment, the outer layer polydopamine will decompose, releasing Dox and IR820 to realize chemotherapy and photothermal therapy. Finally, the ability of DI/MP-MB to efficiently suppress tumor growth was comprehensively assessed and validated both in vitro and in vivo. Noteworthily, the excellent anticancer efficiency by the synergistic effect of gene/photothermal/chemo triple therapy of DI/MP-MB makes it an ideal nanoplatform for tumor therapy and imaging.

Liquids confined between two parallel plates can perform the function of transmission, support, or lubrication in many practical applications, due to which to maintain liquids stable within their working area is very important. However, instabilities may lead to the formation of leaking drops outside the bulk liquid, thus it is necessary to transport the detached drops back without overstepping the working area and causing destructive leakage to the system. In this study, we report a novel and facile method to solve this problem by introducing the wedgelike geometry into the parallel gap to form a parallel-nonparallel combinative construction. Transport performances of this structure were investigated. The criterion for self-propelled motion was established, which seemed more difficult to meet than that in the nonparallel gap. Then, we performed a more detailed investigation into the drop dynamics under squeezing and relaxing modes because the drops can surely return in hydrophilic combinative gaps, whereas uncertainties arose in gaps with a weak hydrophobic character. Therefore, through exploration of the transition mechanism of the drop motion state, a crucial factor named turning point was discovered and supposed to be directly related to the final state of the drops. On the basis of the theoretical model of turning point, the criterion to identify whether a liquid drop returns to the parallel part under squeezing and relaxing modes was achieved. These criteria can provide guidance on parameter selection and structural optimization for the combinative gap, so that the destructive leakage in practical productions can be avoided.

The morphology and dynamics of the pendant drops attached to chemically patterned surfaces (pattern-pinned pendant drops) with different hydrophilic/hydrophobic contrasts were investigated experimentally and numerically. During the experiments, the evolution of the contact angle and the maximum drop volume were found to be different from those of traditional pendant drops, whose contact line is pinned on the edge of the tips (tip-pinned pendant drops), and the deviation is related to both the pattern radius and the wettability contrast. Then, a hypothesis was proposed to illustrate the behavior of the contact line after it reached the pattern boundary, based on the premise that the pattern boundary possessed a certain width or fuzziness. It was concluded that the special phenomena in this case were due to the movement of the contact line, and the maximum contact radius was presented as a key parameter for the pattern-pinned drops, which is directly related to the stability and the maximum volume of the drops. Furthermore, through a simulation study on pattern-pinned pendant drops, the vibration performance of the meniscus was revealed as a superposition of two vibration behaviors including a low-frequency vibration due to the inertia effects and a high-frequency vibration due to the surface tension gradient within the boundary region. In addition, the hypothesis proposed above was also verified. Finally, a forecasting model to predict the maximum contact radius for the pattern-pinned pendant drops was built for different liquids and pattern wettabilities. This allows us to effectively design and optimize chemically patterned surfaces to achieve a desired pinning function or a pendant drop with desired properties.