Radiation-induced liver disease (RILD) poses a major clinical challenge in radiotherapy, transplantation preconditioning, or radiation accidents, yet its pathogenesis is poorly understood due to limited animal models. Here, we establish a translational pig model recapitulating human RILD pathology within 4 weeks post-40 Gy irradiation, featuring veno-occlusive disease (VOD) and centrilobular necrosis. Single-cell atlas analyses identify ferroptosis as a key driver of hepatocyte death during RILD initiation. Ferroptosis inhibition with liproxstatin-1 (Lip-1) not only prevents RILD progression but also reverses histological damage and restores liver function. Mechanistically, Lip-1 treatment restores dysregulated gene expression profiles, particularly associated with hepatocyte ferroptosis, while stimulating hepatic regeneration via coordinated proliferation of hepatocytes and endothelial cells. Our findings establish ferroptosis inhibition as a therapeutic strategy for RILD, demonstrating its dual role in cytoprotection and regeneration. This large animal model provides a robust platform to optimize radiotherapy regimens, improve transplant conditioning, and develop targeted radioprotectants.

Gold nanorods (GNRs) mediated photothermal therapy (PTT) represents a promising technique for cancer treatment, utilizing GNRs in conjunction with near-infrared (NIR) laser irradiation to convert energy into heat. In the present study, we employed PTT to induce apoptosis in pancreatic cancer cells and investigated its underlying mechanisms through quantitative proteomics analysis. Initially, we established that temperatures ranging from 47 to 51 °C significantly enhance cellular apoptosis without inducing necrosis. Furthermore, we identified key pathways involved in cell apoptosis, including apoptosis, oxidative stress, and proteasome pathways. Notably, thermal stimulation also resulted in the upregulation of proteins involved in autophagy, which intriguingly contribute to cellular apoptosis via autophagy regulation. Collectively, our findings demonstrate that GNRs-PTT is an effective therapeutic option for pancreatic cancer and provide a theoretical foundation for the clinical application of photothermal therapy. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (https://proteomecentral.proteomexchange.org) via the iProX partner repository with the dataset identifier PXD058930.

The utilization of alkyl radicals (center dot R) for hypoxic tumor therapy has great prospects due to its O-2-independence and high reactivity. However, correlational initiators for in vivo activation remain scarce. Here, we report that ultrasound excitation of oleic acid-capped BaTiO3 (OA@BaTiO3) can result in an center dot R cascade and hence a means to conquer hypoxic tumors. Mechanistic studies find that the center dot R signal disappears when OA@BaTiO3 undergoes acid washing post-treatment, which is a common procedure for removing the unwanted byproduct BaCO3. Combined with the infrared spectrum analysis, acid treatment was proven to weaken the peaks at 2840-2970 cm(-1) characteristic of -CH2- and terminal -CH3 stretching vibration of OA. There is compelling evidence that high temperature thermal oxidation of OA involves the generation of center dot R. Thus, acid washing is considered to remove the loosely bound yet catalytically active OA. And piezoelectric BaTiO3, a potential electron-hole redox catalyst, can sensitize these OA molecules and disintegrate them to center dot R. This unexpected discovery provides us with a distinctive mentality to seek diverse center dot R initiators for tumor ablation, as well as an additional perspective on the postprocessing of synthetic materials.

Pd-catalyzed chemistry has played a significant role in the growing subfield of bioorthogonal catalysis. However, rationally designing Pd nanocatalysts that show outstanding catalytic activity and good biocompatibility poses a great challenge. Herein, we propose an innovative strategy through exploiting black phosphorous nanosheets (BPNSs) to enhance Pd-mediated bioorthogonal catalytic activity. Firstly, the electron-donor properties of BPNSs enable in situ growth of Pd nanoparticles (PdNPs) on it. Meanwhile, due to the superb capability of reducing PdII , BPNSs can act as hard nucleophiles to accelerate the transmetallation in the decaging reaction process. Secondly, the lone pair electrons of BPNSs can firmly anchor PdNPs on their surface via Pd-P bonds. This design endows Pd/BP with the capability to retard tumor growth by activating prodrugs. This work proposes new insights into the design of heterogeneous transition-metal catalysts (TMCs) for bioorthogonal catalysis.

The antioxidant system of tumor cells severely impairs reactive oxygen species (ROS)-mediated tumor therapy. Despite extensive attempts to attenuate the antioxidant capacity by eliminating ROS scavengers such as glutathione (GSH), nicotinamide adenine dinucleotide phosphate (NADPH) over-expressed in the tumor microenvironment can regenerate GSH from glutathione disulfide (GSSG), hence weakening ROS-induced oxidative damage. Therefore, engineering a nanoplatform capable of depleting both NADPH and GSH is extremely significant for improving ROS-mediated tumor treatment. Herein, a synergetic antioxidant inhibition strategy is proposed to attenuate intracellular antioxidant capacity for hypoxic tumor therapy. In this context, both porous Prussian blue nanoparticles (PPB NPs) and cisplatin prodrug [cis-Pt (IV)] in the nanoplatform can oxidize GSH to directly reduce GSH levels, while PPB NPs also enable NADPH depletion by peroxidase-mimicking to impair GSH regeneration. Furthermore, PPB NPs with catalase-mimicking activity catalyze H2O2 decomposition to alleviate tumor hypoxia, thus reducing the generation of GSH and boosting singlet oxygen (1O2) production by Chlorin e6 (Ce6) for enhancing oxidative damage. Experimental results prove that the nanoplatform, denoted as PPB-Ce6-Pt, can induce remarkable tumor cells apoptosis and ferroptosis. Importantly, a simple loading method and the use of Food Drug Administration (FDA)-approved materials make PPB-Ce6-Pt have great potential for practical applications. STATEMENT OF SIGNIFICANCE: The antioxidant system in tumor cells disables ROS-mediated tumor therapy. Besides, extensive attempts aim at depleting GSH without considering their regeneration. Therefore, we developed a synergetic strategy to attenuate intracellular antioxidant capacity for hypoxic tumor therapy. PPB-Ce6-Pt nanoplatform could not only directly reduce GSH levels but also deplete NADPH by peroxidase-mimicking to impair GSH regeneration. In addition, PPB-Ce6-Pt nanoplatform could catalyze H2O2 decomposition to alleviate tumor hypoxia, thus reducing the generation of GSH and boosting 1O2 production by Chlorin e6 (Ce6) for increasing oxidative damage. Then, intracellular ROS boost and redox dyshomeostasis induced remarkable tumor cells apoptosis and ferroptosis. Importantly, a simple loading method and the use of biosafety materials made the nanoplatform have great potential for practical applications.

Mitigating cellular resistance, which could enhance the sensitivity of tumor cells to treatment, is a promising approach for obtaining better therapeutic outcomes. However, the present designs of materials generally disregard this point, or only focus on a single specific resistance. Herein, a strategy based on a series of cascade reactions aiming to suppress multiple cellular resistances is designed by integrating photothermal and chemotherapy into a mitochondria targeted nanosystem (AuBPs@TD). The intelligent nanosystem is fabricated by modifying gold nanobipyramids (AuBPs) with triphenylphosphonium (TPP) functionalized dichloroacetic acid (DCA). TPP serves as a "navigation system" and facilitates the location of AuBPs@TD in the mitochondria. Moreover, the released DCA promoted by the photothermal effect of AuBPs, as the mitochondrial kinase inhibitor, could inhibit glycolysis, and lead to a repressed expression of heat shock protein 90, which is the main resistance protein in cancer cells against photothermal therapy (PTT). Thus, the photothermal antitumor effect can be significantly improved. For the other cascade passage, the hyperthermal atmosphere depresses the expression of P-glycoprotein, a protein associated with drug resistance, and consequently prevents DCA molecules from being expelled in return. Furthermore, the retained DCA molecules elevate the concentration of intracellular hydrogen peroxide, and due to the peroxidase-like activity of AuBPs, increased intracellular reactive oxygen species could be obtained to accelerate apoptosis. As a result, these cascade reactions lead to significant inhibition of cellular resistance and greatly improve the therapeutic performance. This work paves a new way for suppressing cellular resistance to achieve the desired therapeutic effect.

AbstractSchwerwiegende Nebenwirkungen und mangelhafte therapeutische Wirksamkeit sind die primären Nachteile der derzeitigen Krebsmedikamente. Diese Problematik kann durch gezielte Ansteuerung, das sogenannte Targeting, minimiert werden, jedoch ist die zielgerichtete Wirksamkeit gegenwärtiger Medikamente noch dürftig und benötigt dringend Verbesserungen. Vor diesem Hintergrund fasst dieser Aufsatz zunächst die aktuellen Targetingstrategien in der Krebstherapie hinsichtlich Krebsgewebe und Organellen zusammen. Anschließend analysieren wir das systematische Targeting mit Krebsmedikamenten und schlussfolgern, dass der typische Verlauf eines zielgerichteten Medikaments, das durch intravenöse Injektion verabreicht wurde, eine CTIO‐Kaskade von mindestens vier Schritten durchläuft. Des Weiteren werden zur Sicherstellung einer hohen Gesamt‐Targetingeffizienz die in jedem Schritt benötigten Eigenschaften eines zielgerichteten Wirkstoffs weiter untersucht sowie einige Richtlinien für die Strukturoptimierung zur Gewinnung effektiver Targetingmedikamente offeriert. Zum Schluss beleuchten wir die wesentlichen Probleme und potenziellen Herausforderungen für die künftige Erforschung zielgerichteter Krebstherapien. Ziel dieses Aufsatzes ist es, die Entwicklung von Arzneimitteln für die Hochtechnologiemedizin gegen Krebs aktiv voranzutreiben.

Mitochondria-targeted synergistic therapy, including photothermal (PTT) and photodynamic therapy (PDT), has aroused wide attention due to the high sensitivity to reactive oxygen species (ROS) and heat shock of mitochondria. However, most of the developed nanosystems for the combinatorial functions require the integration of different components, such as photosensitizers and mitochondria-targeted molecules. Consequently, it indispensably requires sophisticated design and complex synthetic procedures. In this work, a well-designed Bi2S3-based nanoneedle, that localizes to mitochondria and produces extra ROS with inherent photothermal effect, was reported by doping of Fe (denoted as FeBS). The engineered intrinsic characteristics certify the capacity of such "one-for-all" nanosystems without additional molecules. The lipophilicity and surface positive charge are demonstrated as crucial factors for specifical mitochondria targeting. Significantly, Fe doping overcomes the disadvantage of the narrow band gap of Bi2S3 to prevent the fast recombination of electron-hole, hence resulting in the generation of ROS for PDT. The "one-for-all" nanoparticles integrate with mitochondria-targeting and synergistic effect of PDT and PTT, thus exhibit enhanced therapeutic effect and inhibit the growth of tumors observably. This strategy may open a new direction in designing the mitochondria-targeted materials and broadening the properties of inorganic semiconductor materials for satisfactory therapeutic outcomes.

X-ray computed tomography (CT) imaging plays an essential role in disease diagnosis due to its noninvasive, painless mode and superior penetration depth. However, the resolution of the soft tissue and minor lesions remains limited. And the disadvantages of conventional contrast agents, such as their inefficient targeting capability, poor biocompatibility, and short circulation times, are considered intractable in clinical use. To overcome these "Gordian knots," nanoparticles (NPs) for CT imaging have been developed. The advantages of NPs are their exceptionally high sensitivity to X-ray, better imaging performance in vivos and even therapeutic effects. In particular, based on various designs, NP contrast agents composed of different materials integrate multiple imaging modalities, make up for the inadequacy of a single imaging type, and thus provide more accurate information for diagnosis. This review focuses on NPs for X-ray CT imaging and their multifunctional designs. Some perspectives of crucial problems and prospective challenges are also discussed.

Tumor hypoxia severely limits the therapeutic effects of photodynamic therapy (PDT). Although many methods for oxygen generation exist, substantial safety concerns, spatiotenporal uncontrollability, limited efficacy, and complicated procedures have compromised their practical application. Here, we demonstrate a biocompatiable all-in-one organic semiconductor to provide a photoxidation catalysis mechanism of action. A facile method is developed to produce gram-level C5 N2 nanoparticles (NPs)-based organic semiconductor. Under 650 nm laser irradiation, the semiconductor split water to generate O2 and simultaneously produce singlet oxygen (1 O2 ), showing that the photocatalyst for O2 evolution and the photosensitizer (PS) for 1 O2 generation could be synchronously achieved in one organic semiconductor. The inherent nucleus targeting capacity endows it with direct and efficient DNA photocleavage. These findings pave the way for developing organic semiconductor-based cancer therapeutic agents.

Severe side effects and poor therapeutic efficacy are the main drawbacks of current anticancer drugs. These problems can be mitigated by targeting, but the targeting efficacy of current drugs is poor and urgently needs improvement. Taking this into consideration, this Review first summarizes the current targeting strategies for cancer therapy in terms of cancer tissue and organelles. Then, we analyse the systematic targeting of anticancer drugs and conclude that a typical journey for a targeted drug administered by intravenous injection is a CTIO cascade of at least four steps. Furthermore, to ensure high overall targeting efficacy, the properties of a targeting drug needed in each step are further analysed, and some guidelines for structure optimization to obtain effective targeting drugs are offered. Finally, some viewpoints highlighting the crucial problems and potential challenges of future research on targeted cancer therapy are presented. This review could actively promote the development of precision medicine against cancer.

Intracellular targeting has the same potential as tissue targeting to increase therapy efficacy, especially for drugs that are toxic to DNA. By adjusting intracellular traffic, we developed a novel direct‐nucleus‐delivery platform based on C 5 N 2 nanoparticles (NPs). Supramolecular interactions of C 5 N 2 NPs with the cell membrane enhanced cell uptake; abundant edge amino groups promoted fast and effective rupture of early endosomes; and the appropriate size of the NPs was also crucial for size‐dependent nuclear entry. As a proof of concept, the platform was not only suitable for the effective delivery of molecular drugs/dyes (doxorubicin, hydroxycamptothecine, and propidium iodide) and MnO 2 nanoparticles to the nucleus, but was also photoresponsive for nucleus‐targeting photothermal therapy (PTT) and photodynamic therapy (PDT) to further greatly increase anticancer efficacy. This strategy might open the door to a new generation of nuclear‐targeted enhanced anticancer therapy.

Intracellular targeting has the same potential as tissue targeting to increase therapy efficacy, especially for drugs that are toxic to DNA. By adjusting intracellular traffic, we developed a novel direct-nucleus-delivery platform based on C5N2 nanoparticles (NPs). Supramolecular interactions of C5N2 NPs with the cell membrane enhanced cell uptake; abundant edge amino groups promoted fast and effective rupture of early endosomes; and the appropriate size of the NPs was also crucial for size-dependent nuclear entry. As a proof of concept, the platform was not only suitable for the effective delivery of molecular drugs/dyes (doxorubicin, hydroxycamptothecine, and propidium iodide) and MnO2 nanoparticles to the nucleus, but was also photoresponsive for nucleus-targeting photothermal therapy (PTT) and photodynamic therapy (PDT) to further greatly increase anticancer efficacy. This strategy might open the door to a new generation of nuclear-targeted enhanced anticancer therapy.

OBJECTIVE:To investigate the effect of lead selenide nanocrystals on hematopoietic system and bone marrow micronucleus rate of rats. METHOD:Specific pathogen free SD rats were randomly divided into 4 groups (8 rats in each group), and injected with of 0 (control group), 10 (low dose group), 20 (middle dose group), 30 mg/kg (high dose group) nanocrystalline PbSe, respectively. Seven weeks after injection, the blood was taken from rats for routine index detection; the number of micronucleus cells per 1000 polychromatic erythrocyte from bone marrow was counted. RESULTS:White blood cell (WBC), lymphocyte (LYM) count in low dose group rats, and WBC, LYM, granulocyte (GRN), monocytes (MOD) counts in high dose group significantly increased compared to those of control group. LYM% ratio decreased while GRN% ratio increased along with the increase of exposure dosage. Compared with those of the control group, levels of erythrocyte mean corpuscular volume (MCV) in low dose group, hemoglobin (HGB), red blood cell specific volume (HCT), MCV in middle dose group and red blood cell (RBC), HGB, HCT, MCV in high dose group, were markedly decreased. Red blood cell distribution width (RDW), blood platelet (PLT) levels in three exposure groups of were higher than those in control group. Marrow micronucleus test results showed that, the micronucleus rate rise in mid dose and high dose group compared with the control group, suggesting that nanocrystalline PbSe has genetic toxicity on rats. CONCLUSIONS:Nano PbSe can lead to changes in blood routine index and bone marrow micronucleus rate, and its toxicity was positively related to the dosage.

We demonstrate a high-intensity sonication route to the synthesis of supported noble metal catalytic materials.The in situ produced metal or bimetal nanoparticles from the reduction of precursor using NaBH 4 were uniformly deposited onto a variety of supports,such as graphene,carbon nanotubes,metal oxides (cerium oxide,hematite,titanium oxide),with the aid of ultrasound.The as-prepared catalysts were characterized in detail by means of X-ray photoelectron spectroscopy,transmission electron microscope,energy-dispersive X-ray spectrometer,and selected-area electron diffraction.It was observed that the metal nanoparticles with small sizes and narrow diameter distributions were highly distributed on the surfaces of the supports.In addition,the size of the particles could be readily tuned by manipulating the processing parameters including the metal loading level,the precursor concentration and the amplitude of the sonic power.Of particular interest is that this method offers an effective strategy to preparing supported noble metal nanocatalysts.