Bismuth sulfide (Bi S ) nanomaterials are emerging as a promising theranostic platform for computed tomography imaging and photothermal therapy of cancer. Herein, the photothermal properties of Bi S nanorods (NRs) were unveiled to intensely correlate to their intrinsic deep-level defects (DLDs) that potentially could work as electron-hole nonradiative recombination centers to promote phonon production, ultimately leading to photothermal performance. Bi S -Au heterojunction NRs were designed to hold more significant DLD properties, exhibiting more potent photothermal performance than Bi S NRs. Under 808 nm laser irradiation, Bi S -Au NRs could trigger higher cellular heat shock protein 70 expression and more apoptotic cells than Bi S NRs, and caused severe cell death and tumor growth inhibition, showing great potential for photothermal therapy of cancer guided by computed tomography imaging.

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.

Nitric oxide (NO) molecular messenger can reverse the multidrug resistance (MDR) effect of cancer cells through reducing P-glycoprotein (P-gp) expression, beneficial for creating a favorable microenvironment for the treatment of doxorubicin (Dox)-resistant cancer cells. Development of sophisticated nanosystems to programmably release NO and Dox becomes an efficient strategy to overcome the MDR obstacles and achieve promising therapeutic effects in Dox-resistant cancer. Herein, a NO stimulated nanosystem was designed to engineer a significant time gap between NO and Dox release, promoting MDR cancer therapy. A o-phenylenediamine-containing lipid that can hydrolyze in response to NO was embedded in the phospholipid bilayer structure of liposome to form NO-responsive liposome, which could further encapsulate L-arginine (L-Arg)/Doxloaded gold@copper sulfide yolk−shell nanoparticls ( AD Au@CuS YSNPs) to form ADL Au@CuS YSNPs. Under 808 nm laser irradiation, the unique resonant energy transfer (RET) process and reactive oxygen species (ROS) generation in the confined space of ADL Au@CuS YSNPs could effectively convert L-Arg into NO, regionally destabilizing the phospholipid bilayer structure, as a result of NO release. However, at this early stage Dox could not be released from YSNPs due to the molecular scaffold limit. As the NO release progressed, the NO-responsive liposome layer was deteriorated more severely, allowing Dox to escape. This NO and Dox sequential release of ADL Au@CuS YSNPs could significantly inhibit P-gp expression and enhance Dox accumulation in Dox-resistant MCF-7/ADR cells, leading to promising in vitro and in vivo therapeutic effects and presenting their great potential for MDR cancer therapy.

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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.

to our best knowledge, there is no report focusing on the photodynamic performance of Bi-based NMs yet. Theoretically, as a narrow bandgap semiconductor, [2a] Bi 2 S 3 can be excited by NIR laser to generate free electrons in the conduction band (CB) and holes in the valence band (VB), which can react with oxygen and water to form superoxide and hydroxyl radicals, respectively, for potential NIR-activated photodynamic therapy (PDT). However, in view of the fast electron-hole recombination, above reactive oxygen species (ROS) production is dramatically suppressed. Thus, development of sophisticated Bi 2 S 3based nanosystems to enable efficient electron-hole separation potentially can endow Bi 2 S 3 with the photodynamic performance, affording combination with photothermal therapy (PTT) and CT imaging. Besides the low ROS production efficiency, the innate antioxidant defense capability of tumor cells is usually another obstacle to effective PDT because the overexpressed phase II enzymes in tumor cells can provide sustainable protection against elevated ROS stress. [6] Heme oxygenase (HO-1), the most important phase II enzyme, has been known to be highly expressed in solid tumor, [6,7] playing a critical role in antioxidant defense. [8] Once cells are attacked by ROS, the redox homeostasis is disturbed and HO-1 can catalyze the heme molecule to generate a series of antioxidants (such as biliverdin, carbon monoxide, and ferrous iron), which are the most potent endogenous scavengers of ROS. It has been reported that zinc protoporphyrin IX (ZP) can work as a potent HO-1 inhibitor to suppress the HO-1 activity because ZP is a heme derivative and can more competitively bind to the active site of HO-1 enzyme than heme. [9] Thus, ZP potentially can be employed to inhibit HO-1 activity for strengthening PDT effect.The staggered energy band edges in heterogeneous materials can efficiently facilitate electron-hole separation. [10] The lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO) energies of ZP are −1.48 and 0.63 V versus standard hydrogen electrode (SHE), respectively, [11] while the CB and VB energies of Bi 2 S 3 are 0.09-0.12 and 1.41-1.47 V versus SHE, respectively, [12] which means that Bi 2 S 3 can form a type-II heterostructure with ZP. [13] When Bismuth (Bi)-based nanomaterials (NMs) are widely used for computed tomography (CT) imaging guided photothermal therapy, however, the photodynamic property is hardly exhibited by these NMs due to the fast electron-hole recombination within their narrow bandgap. Herein, a sophisticated nanosystem is designed to endow bismuth sulfide (Bi 2 S 3 ) nanorods (NRs) with potent photodynamic property. Zinc protoporphyrin IX (ZP) is linked to Bi 2 S 3 NRs through a thermoresponsive polymer to form BPZP nanosystems. The stretching ZP could prebind to the active site of heme oxygenase-1 overexpressed in cancer cells, suppressing the cellular antioxidant defense capability. Upon NIR laser irradiation, the heat released from Bi 2 S 3 NRs cou...

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.

Silver (Ag)-based nanoparticles (NPs) with a high potential of Ag+ release have been known to be capable of promoting bacteria inactivation and the wound healing process; however, keeping a steady flux of high levels of Ag+ in Ag-based NPs is still challenging. Herein, a novel strategy in terms of altering the intrinsic electronic structure of Ag NPs was attempted to facilitate Ag oxidation and boost the Ag+ flux, as results of improved antibacterial and wound healing performance of Ag NPs. Gold (Au), platinum (Pt), and palladium (Pd) were doped into Ag NPs to tune their d band centers to upshift toward the Fermi level, and the formed Pd–Ag alloy NPs showed the largest shift, followed by Pt–Ag and Au–Ag NPs, as determined by density function theory calculation and ultraviolet photoemission spectroscopy measurement. Further X-ray photoelectron spectroscopy analysis indicates that a larger upshift could induce less electron filling in the antibonding orbital and a higher Ag oxidation level, leading to the more remarkable Ag+ release as determined by inductively coupled plasma optical emission spectrometry. All these alloy Ag NPs could more efficiently inhibit bacterial growth and accelerate the wound healing process than pure Ag NPs, and their antibacterial activity and wound healing performance were progressively proportional to the upshift values of the d band center. Taken together, tuning the d band center to upshift toward the Fermi level becomes a feasible strategy for designing therapeutic Ag-based NPs with a promising antibacterial and wound healing performance.