Bladder cancer (BCa) is the most costly solid tumor owing to its high recurrence. Relapsed cancer is known to acquire chemoresistant features after standard intravesical chemotherapy. This cancer state is vulnerable to ferroptosis, which occurs when lipid peroxides generated by iron metabolism accumulate to lethal levels. Increasing the labile iron pool (LIP) by iron oxide nanoparticles (IONPs) promises to inhibit chemoresistant BCa (CRBCa), but systemically administered IONPs do not sufficiently accumulate at the tumor site. Therefore, their efficacy is weakened. Here, we present a three-tier delivery strategy through a mucoadhesive hydrogel platform conveying hyaluronic acid-coated IONPs (IONP−HA). When instilled, the hydrogel platform first adhered to the interface of the tumor surface, sustainably releasing IONP−HA. Subsequently, the tumor stiffness and interstitial fluid pressure were reduced by photothermal therapy, promoting IONP−HA diffusion into the deep cancer tissue. As CRBCa expressed high levels of CD44, the last delivery tier was achieved through antibody-mediated endocytosis to increase the LIP, ultimately inducing ferroptosis. This three-tiered strategy delivered the IONPs stepwise from anatomical to cellular levels and increased the iron content by up to 50-fold from that of systematic administration, which presents a potential regimen for CRBCa.

Traditional hydrogel sensors containing MXenes as a conductive substrate will inevitably face the problem of excessive stacking of MXene nanosheets, which limits electron transport, thus reducing conductivity and sensitivity. Moreover, existing MXene hydrogels generally exhibit poor mechanical properties and fragility. In addition, it is necessary to prepare degradable electronic skins for reducing environmental pollution and recycling energy materialsMXene. How to find a balance between mechanical properties and degradation properties is a challenge. In this work, we overcome this challenge by combining a dynamic covalent strategy and establishing a self-modified interlocked structure. A biodegradable physically cross-linked hydrogel (OMDDHordered MXene dynamic degradable hydrogel) is constructed, and a highly interconnected three-dimensional (3D) MXene@CS-Pba network is prepared, thus endowing the sensor with excellent conductivity (24 × 10–4 S cm–1). For excellent mechanical properties, dynamic covalent interactions, hydrogen-bonding interactions between the dual networks, and chain entanglement of poly­(vinyl alcohol) (PVA) totally build interlocked structures, thus endowing the hydrogel with excellent mechanical strength (1000 kPa). In an acidic environment, the dynamic covalent bond is broken, and the chain entanglement of PVA is also disentangled due to the disruption of the electrostatic equilibrium, resulting in the release of MXene for recycling (recycling conductivity: 22 × 10–4 S cm–1). Undoubtedly, we exhibit a strategy to construct ordered and degradable MXene hydrogels possessing excellent conductivity, high mechanical strength, and degradation performance, which lays the sensors’ wide applications in smart devices.

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Heatstroke is a life-threatening illness that is characterised by a core body temperature >40°C and central nervous system dysfunction. Acute kidney injury (AKI) is a common complication of heatstroke, and the mitochondrial apoptotic pathway has been demonstrated to be one of the leading causes of tissue damage and cell death in AKI. Curcumin is a phenol that is extracted from turmeric and demonstrates anti-apoptotic properties. To test if curcumin can protect the kidney from injury caused by heat stress, the effect of curcumin administration on renal injury and apoptosis of renal tissue was examined in a rat model of dry-heat environment. A total of 50 Sprague-Dawley rats were randomly divided into five groups (n=10): Standard temperature control, dry-heat control and curcumin treatment groups (50, 100 and 200 mg/kg groups). After exposure to a dry-heat environment for 150 min, the rats were anesthetized and euthanized. Blood, urine and renal tissue were collected to quantify the expression of specific mitochondrial apoptosis-related molecules. Curcumin pre-treatment decreased blood urea nitrogen and serum creatinine, urinary kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin levels compared with the dry-heat control group. Curcumin was also revealed to downregulate c-Jun N-terminal kinases (JNK), cytochrome c, caspase-3 and caspase-9 expression upon treatment with 100 and 200 mg/kg curcumin, which may result in inhibition of the mitochondrial apoptotic pathway in renal cells. The current study revealed that Curcumin may to have potential for preventing heatstroke-induced AKI.