Gold (Au) core@void@copper sulfide (CuS) shell (Au-CuS) yolk-shell nanoparticles (YSNPs) were prepared in the present study for potential chemo-, photothermal, and photodynamic combination therapy, so-called "chemophototherapy". The resonance energy transfer (RET) process was utilized in Au-CuS YSNPs to achieve both enhanced photothermal and photodynamic performance compared with those of CuS hollow nanoparticles (HNPs). A series of Au nanomaterials as cores that had different localized surface plasmon resonance (LSPR) absorption peaks at 520, 700, 808, 860, and 980 nm were embedded in CuS HNPs to screen the most effective Au-CuS YSNPs according to the RET process. Thermoresponsive polymer was fabricated on these YSNPs' surface to allow for controlled drug release. Au-CuS and Au-CuS YSNPs were found capable of inducing the largest temperature elevation and producing the most significant hydroxyl radicals under 808 and 980 nm laser irradiation, respectively, which could accordingly cause the most severe 4T1 cell injury through oxidative stress mechanism. Moreover, doxorubicin-loaded (Dox-loaded) P(NIPAM-co-AM)-coated Au-CuS (p-Au-CuS@Dox) YSNPs could more efficiently kill cells than unloaded particles upon 980 nm laser irradiation. After intravenous administration to 4T1 tumor-bearing mice, p-Au-CuS YSNPs could significantly accumulate in the tumor and effectively inhibit the tumor growth after 980 nm laser irradiation, and p-Au-CuS@Dox YSNPs could further potentiate the inhibition efficiency and exhibit excellent in vivo biocompatibility. Taken together, this study sheds light on the rational design of Au-CuS YSNPs to offer a promising candidate for chemophototherapy.
Wound healing is a complex and sequential biological process that involves multiple stages. Although various nanomaterials are applied to accelerate the wound healing process, only a single stage is promoted during the process, lacking hierarchical stimulation. Herein, hollow CeO2 nanoparticles (NPs) with rough surface and l‐arginine inside (AhCeO2 NPs) are developed as a compact and programmable nanosystem for sequentially promoting the hemostasis, inflammation, and proliferation stages. The rough surface of AhCeO2 NPs works as a nanobridge to rapidly closure the wounds, promoting the hemostasis stage. The hollow structure of AhCeO2 NPs enables the multireflection of light inside particles, significantly enhancing the light harvest efficiency and electron–hole pair abundance. Simultaneously, the porous shell of AhCeO2 NPs facilitates the electron–hole separation and reactive oxygen species production, preventing wound infection and promotion wound healing during the inflammation stage. The enzyme mimicking property of AhCeO2 NPs can alleviate the oxidative injury in the wound, and the released l‐arginine can be converted into nitric oxide (NO) under the catalysis of inducible NO synthase, both of which promote the proliferation stage. A series of in vitro and in vitro biological assessments corroborate the effectiveness of AhCeO2 NPs in the wound healing process.
The {101}-{001} surface heterojunction constructed on polyhedral titanium dioxide (TiO) nanocrystals has recently been proposed to be favorable for the efficient electron-hole spatial separation due to the preferential accumulation of electron and hole on {101} and {001} facets, respectively. The formed free electron and hole can promote reactive oxygen species (ROS) production, which potentially can be used for inactivation of bacteria. In the present study, a series of truncated octahedral bipyramid TiO nanocrystals (T1, T2, T3, and T4) coexposed with {101} and {001} facets were prepared to form various ratios of {101} to {001} facet for optimization of electron-hole spatial separation efficiency. All these polyhedral TiO nanocrystals could more significantly produce ROS than spherical TiO nanocrystals (Ts), exhibiting the higher antibacterial activity against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria under simulated sunlight irradiation. Among these polyhedral TiO nanocrystals, T3 with a {101}/{001} ratio of 1.78 was found to be the best one showing the highest ROS and the most potent antibacterial performance. Scanning electron microscope images of bacteria displayed that the surface membrane structure of both E. coli and S. aureus bacteria was influenced to different extents by these TiO nanocrystals, where T3 caused the most severe membrane damage. The molecular mechanism underlying the high antibacterial activity of TiO nanocrystals was ascribed to activation of oxidative stress as evidenced by intracellular ROS production, glutathione depletion, and membrane lipid peroxidation in bacteria. The surface heterojunction as a completely new strategy holds great promise to develop effective antibacterial nanomaterials.
Simulated sunlight has promise as a light source able to alleviate the severe pain associated with patients during photodynamic therapy (PDT); however, low sunlight utilization efficiency of traditional photosensitizers dramatically limits its application. Titanium-dioxide-nanoparticle-gold-nanocluster-graphene (TAG) heterogeneous nanocomposites are designed to efficiently utilize simulated sunlight for melanoma skin cancer PDT. The narrow band gap in gold nanoclusters (Au NCs), and staggered energy bands between Au NCs, titanium dioxide nanoparticles (TiO NPs), and graphene can result in efficient utilization of simulated sunlight and separation of electron-hole pairs, facilitating the production of abundant hydroxyl and superoxide radicals. Under irradiation of simulated sunlight, TAG nanocomposites can trigger a series of toxicological responses in mouse B16F1 melanoma cells, such as intracellular reactive oxygen species production, glutathione depletion, heme oxygenase-1 expression, and mitochondrial dysfunctions, resulting in severe cell death. Furthermore, intravenous or intratumoral administration of biocompatible TAG nanocomposites in B16F1-tumor-xenograft-bearing mice can significantly inhibit tumor growth and cause severe pathological tumor tissue changes. All of these results demonstrate prominent simulated sunlight-mediated PDT effects.
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