Synergistic Oxidative Damage with Gene Therapy Potentiates Targeted Sterilization of Broad-Spectrum Microorganisms

Nanoparticle-based approaches addressed the barriers to antibiotic resistance faced by traditional antimicrobial agents. However, nanotherapies against multibacterial infections still suffered from the lack of broad-spectrum targeting ability and the mono-inhibition pathway. In this study, a multimodality therapeutic nanoplatform (denoted as Asza) is introduced, which combines specific recognition, synergistic oxidative damage, and gene therapy, to effectively inhibit the emergence of bacterial resistance, achieving broad-spectrum sterilization activity against two Gram-positive (B. subt, S. epider) and two Gram-negative bacteria (E. coli, E. aero). In addition to the oxidative damage generated from gold nanoclusters, DNA aptamer, and CRISPR-Cas modules are combined in the Asza to recognize multiple bacteria and cleave the ftsz gene with high specificity, allowing precision treatment of multibacterial infections without damaging surrounding healthy cells. Furthermore, multimodal antimicrobial strategies can reduce the risk of the generation of bacterial resistance to single-modality therapy and significantly boost the efficiency of antibacterial therapy. This study offers a promising approach to advance the applications of nanomaterials in clinical antimicrobial therapy.     

Cascade-Responsive “Oxidative Stress Amplifiers” Simultaneously Destroy Lysosomes and Co-Deliver CRISPR/Cas9 to Enhance Oxidative Damage in Tumor

Amplifying intracellular oxidative stress by organelle-targeted reactive oxygen species (ROS) production combined with tumor cell-specific gene disruption is a promising strategy for tumor treatment. However, due to the vulnerability of CRISPR/Cas9 ribonucleoproteins (RNPs) to ROS, co-delivery of CRISPR/Cas9 RNPs and ROS generators to enhance the sensitivity of tumor cells to oxidative stress remains challenging. Herein, a cascade-responsive “oxidative stress amplifier” (named DR-TAF-pHT/FA) is proposed, which can successively respond to cathepsin B, localized laser irradiation and ATP to generate ROS on the lysosomal membrane of tumor cells and release Cas9/sgNrf2 RNPs for efficient gene disruption. It is demonstrated that, under near infrared (NIR) irradiation, DR-TAF-pHT/FA achieves targeted rupture of lysosomal membranes, inducing significant intracellular oxidative stress. Meanwhile, due to the protective function of TAF coating (TA-Fe³⁺ coordination self-assembled networks), Cas9/sgNrf2 RNPs can safely escape into the cytoplasm and be released in response to ATP, further amplifying oxidative stress and promoting tumor cell apoptosis through efficient Nrf2 gene disruption. Treatment with DR-TAF-pHT/FA + NIR significantly improves tumor ablation efficiency and extends median survival time (over 70 days) in Hela xenograft models. This “oxidative stress amplifier” provides a new paradigm for multimodal and synergistic tumor therapy through precise lysosomal membrane bursting together with efficient Nrf2 gene disruption.     

Self-Healing and -Repair of Nanomechanical Damages in Lead Halide Perovskites

Recovery from damage in materials helps extend their useful lifetime and of devices that contain them. Given that the photodamages in HaP materials and based devices are shown to recover, the question arises if this also applies to mechanical damages, especially those that can occur at the nanometer scale, relevant also in view of efforts to develop flexible HaP-based devices. Here, this question is addressed by poking HaP single crystal surfaces with an atomic force microscope (AFM) tip under both ultra-high vacuum (UHV) and variably controlled ambient water vapor pressure conditions. Sequential in situ AFM scanning allowed real-time imaging of the morphological changes at the damaged sites. Using methylammonium (MA) and cesium (Cs) variants for A-site cations in lead bromide perovskites, the experiments show that nanomechanical damages on methylammonium lead bromide (MAPbBr₃) crystals heal an order of magnitude faster than Cs-based ones in UHV. However, surprisingly, under ≥40% RH conditions, cesium lead bromide (CsPbBr₃) shows MAPbBr₃-like fast healing kinetics. Direct evidence for ion solvation on CsPbBr₃ is presented, leading to the formation of a surface hydration layer. The results imply that moisture improves the ionic mobility of degradation components and leads to water-assisted improved healing, i.e., repair of nanomechanical damages in the HaPs.     

Ultra-Strong Comprehensive Radiation Effect Tolerance in Carbon Nanotube Electronics

Carbon nanotube (CNT) field-effect transistors (FETs) have been considered ideal building blocks for radiation-hard integrated circuits (ICs), the demand for which is exponentially growing, especially in outer space exploration and the nuclear industry. Many studies on the radiation tolerance of CNT-based electronics have focused on the total ionizing dose (TID) effect, while few works have considered the single event effects (SEEs) and displacement damage (DD) effect, which are more difficult to measure but may be more important in practical applications. Measurements of the SEEs and DD effect of CNT FETs and ICs are first executed and then presented a comprehensive radiation effect analysis of CNT electronics. The CNT ICs without special irradiation reinforcement technology exhibit a comprehensive radiation tolerance, including a 1 × 10⁴ MeVcm² mg⁻¹ level of the laser-equivalent threshold linear energy transfer (LET) for SEEs, 2.8 × 10¹³ MeV g⁻¹ for DD and 2 Mrad (Si) for TID, which are at least four times higher than those in conventional radiation-hardened ICs. The ultrahigh intrinsic comprehensive radiation tolerance will promote the applications of CNT ICs in high-energy solar and cosmic radiation environments.