Yuqi Huang’s research while affiliated with Shanghai University and other places

The programmed cell death (PCD) pathway removes functionally insignificant, infection-prone, or potentially tumorigenic cells, underscoring its important role in maintaining the stability of the internal environment and warding off cancer and a host of other diseases. PCD includes various forms, such as apoptosis, copper death, iron death, and cellular pyroptosis. However, emerging solid-state electron-mediated Z-scheme heterostructured semiconductor nanomaterials with high electron-hole (e–h⁺) separation as a new method for inducing PCD have not been well studied. We synthesize the Bi2S3-Bi2O3-Au-PEG nanorods (BB-A-P NRs) Z-scheme heterostructured semiconductor has a higher redox capacity and biocompatibility. Firstly, the BB-A-P NRs are excited by near-infrared (NIR) light, which mimics the action of catalase by supplying oxygen (O2) and converting it to a single-linear state of oxygen (¹O2) via e–h⁺ transfer. Secondly, they react with hydrogen peroxide (H2O2) and water (H2O) in tumor to produce hydroxyl radicals (•OH), inducing apoptosis. Intriguingly, the Caspase-1/Gasdermin D (GSDMD)-dependent conventional pyroptosis pathway induced cellular pyroptosis activated by apoptosis and reactive oxygen species (ROS) which causes the intense release of damage associated molecular patterns (DAMPs), leading to the inflammatory death of tumor cells. This, in turn, activates the immunological environment to achieve immunogenic cell death (ICD). BB-A-P enables computed tomography imaging, which allows for visualization of the treatment. BB-A-P activated dual PCD can be viewed as an effective mode of cell death that coordinates the intracellular environment, and the various pathways are interrelated and mutually reinforcing which shows promising therapeutic effects and provides a new strategy for eliminating anoxic tumors. Graphical abstract

Noise‐induced hearing loss (NIHL), a prevalent sensory disability affecting a majority of the global population, is dominantly induced by mitochondrial dysfunction and oxidative stress, but no effective therapeutic strategy is available. Herein, the potential of a 2D catalytic niobium carbide (Nb2C) MXenzyme is investigated as a nanomedicine for treating NIHL by scavenging reactive oxygen species (ROS). The findings reveal that 2D Nb2C MXenzyme effectively eliminates free radicals, resulting in a substantial reduction of ROS in House Ear Institute‐Organ of Corti 1 (HEI‐OC1) cells treated with hydrogen peroxide (H2O2). Additionally, the 2D Nb2C MXenzyme demonstrates significant protection on hair cells by preventing cytotoxicity and apoptosis induced by H2O2. In vivo experiments further support the efficacy of the 2D Nb2C MXenzyme in restoring hearing impairment caused by extensive noise exposure. Specifically, it restores the raised amplitude of Wave I in auditory brainstem response (ABR) records and promotes the recovery of damaged ribbon synapses in inner hair cells. Notably, the therapeutic effect of the 2D Nb2C MXenzyme is attributed to its ability to suppress cochlear oxidative stress evidenced by immunohistochemical analysis. This research provides a new approach for treating hearing loss‐related ear diseases by utilizing catalytic biomaterials and nanomedicine with enzyme‐mimicking properties.

Cuproptosis, a recently discovered copper‐dependent cell death, presents significant potential for the development of copper‐based nanoparticles to induce cuproptosis in cancer therapy. Herein, a unique ternary heterojunction, denoted as HACT, composed of core–shell Au@Cu2O nanocubes with surface‐deposited Titanium Dioxide quantum dots and modified with hyaluronic acid is introduced. Compared to core–shell AC NCs, the TiO2/Au@Cu2O exhibits improved energy structure optimization, successfully separating electron‐hole pairs for redox use. This optimization results in a more rapid generation of singlet oxygen and hydroxyl radicals triggering oxidative stress under ultrasound radiation. Furthermore, the HACT NCs initiate cuproptosis by Fenton‐like reaction and acidic environment, leading to the sequential release of cupric and cuprous ions. This accumulation of copper induces the aggregation of lipoylated proteins and reduces iron‐sulfur proteins, ultimately initiating cuproptosis. More importantly, HACT NCs show a tendency to selectively target cancer cells, thereby granting them a degree of biosecurity. This report introduces a ternary heterojunction capable of triggering both cuproptosis and oxidative stress‐related combination therapy in a stimulus‐responsive manner. It can energize efforts to develop effective melanoma treatment strategies using Cu‐based nanoparticles through rational design.

Zinc oxide nanoparticles (ZnO NPs) stand as among the most significant metal oxide nanoparticles in trigger the formation of reactive oxygen species (ROS) and induce apoptosis. Nevertheless, the utilization of ZnO NPs has been limited by the shallowness of short-wavelength light and the constrained production of ROS. To overcome these limitations, a strategy involves achieving a red shift towards the near-infrared (NIR) light spectrum, promoting the separation and restraining the recombination of electron-hole (e⁻-h⁺) pairs. Herein, the hybrid plasmonic system Au@ZnO (AZ) with graphene quantum dots (GQDs) doping (AZG) nano heterostructures is rationally designed for optimal NIR-driven cancer treatment. Significantly, a multifold increase in ROS generation can be achieved through the following creative initiatives: (i) plasmonic Au nanorods expands the photocatalytic capabilities of AZG into the NIR domain, offering a foundation for NIR-induced ROS generation for clinical utilization; (ii) elaborate design of mesoporous core-shell AZ structures facilitates the redistribution of electron-hole pairs; (iii) the incorporation GQDs in mesoporous structure could efficiently restrain the recombination of the e⁻-h⁺ pairs; (iv) Modification of hyaluronic acid (HA) can enhance CD44 receptor mediated targeted triple-negative breast cancer (TNBC). In addition, the introduced Au NRs present as catalysts for enhancing photothermal therapy (PTT), effectively inducing apoptosis in tumor cells. The resulting HA-modified AZG (AZGH) exhibits efficient hot electron injection and e⁻-h⁺ separation, affording unparalleled convenience for ROS production and enabling NIR-induced PDT for the cancer treanment. As a result, our well-designed mesoporous core-shell AZGH hybrid as photosensitizers can exhibit excellent PDT efficacy. Supplementary Information The online version contains supplementary material available at 10.1186/s12951-024-02530-4.