Leveraging Radiation-triggered Metal Prodrug Activation Through Nanosurface Energy Transfer for Directed Radio-chemo-immunotherapy.

Metal-based drugs currently dominate the field of chemotherapeutic agents; however, achieving the controlled activation of metal prodrugs remains a substantial challenge. Here, we propose a universal strategy for the radiation-triggered activation of metal prodrugs via nanosurface energy transfer (NSET). The core-shell nanoplatform (Ru-GNC) is composed of gold nanoclusters (GNC) and ruthenium (Ru)-containing organic-inorganic hybrid coatings. Upon X-ray irradiation, chemotherapeutic Ru (II) complexes were released in a controlled manner through a unique NSET process involving the transfer of photoelectron energy from the radiation-excited Ru-GNCs to the Ru-containing hybrid layer. In contrast to the traditional radiation-triggered activation of prodrugs, such an NSET-based system ensures that the reactive species in the tumor microenvironment are present in sufficient quantity and are not easily quenched. Additionally, ultrasmall Ru-GNCs preferably target mitochondria and profoundly disrupt the respiratory chain upon irradiation, leading to radiosensitization by generating abundant reactive oxygen species. Consequently, Ru-GNC-directed radiochemotherapy induces immunogenic cell death, resulting in significant therapeutic outcomes when combined with the programmed cell death-ligand 1 (PD-L1) checkpoint blockade. This NSET strategy represents a breakthrough in designing radiation-triggered nanoplatforms for metal-prodrug-mediated cancer treatment in an efficient and controllable manner.

X-ray-controllable release of carbon monoxide potentiates radiotherapy by ultrastable hybrid nanoreservoirs.

Carbon monoxide (CO) exhibits unique abilities in sensitizing cancer radiotherapy (RT). However, the development of a highly stable CO-delivery nanosystem with sustained CO release in tumor tissues and the prevention of CO leakage into normal tissues remains a challenge. Herein, an organic-inorganic hybrid strategy is proposed to create ultrastable CO nanoreservoirs by locking an unstable iron carbonyl (FeCO) prodrug in a stable mesoporous silica matrix. Different from traditional FeCO-loading nanoplatforms, FeCO-bridged nanoreservoirs not only tethered labile FeCO in the framework to prevent unwanted FeCO leakage, but also achieved sustained CO release in response to X-ray and endogenous H2O2. Importantly, FeCO-bridged nanoreservoirs exhibited the sequential release of CO and Fe2+, thereby performing highly efficient chemodynamic therapy. Such a powerful combination of RT, gas therapy, and chemodynamic therapy boosts robust immunogenic cell death, thus enabling the elimination of deeply metastatic colon tumors with minimal side effects. The proposed organic-inorganic hybrid strategy opens a new window for the development of stable nanoreservoirs for the on-demand delivery of unstable gases and provides a feasible approach for the sequential release of CO and metal ions from metal carbonyl complexes.

Potential of a sensitive uric acid biosensor fabricated using hydroxyapatite nanowire/reduced graphene oxide/gold nanoparticle.

In this study, a ternary nanocomposite consisting of gold nanoparticles (AuNPs), hydroxyapatite (HAP) nanowires, and reduced graphene oxide (rGO) is synthesized by a simple one-step hydrothermal method, which is used to modify glassy carbon electrode (GCE) for detecting uric acid. The nanocomposite is characterized through various methods such as scanning electron microscopy, transmission electron microscopy, and X-ray diffraction. Electrochemical measurements of the modified GCE are performed in a conventional three-electrode system. Experimental results show that the obtained HAP nanowire and rGO are mixed homogeneously, and the AuNPs are deposited into this matrix. The GCE modified by the nanocomposites have superior electrocatalytic activities for uric acid. The peak current intensities of UAO (uricase)/HAP-rGO/AuNPs sensing system linearly increase as the uric acid concentration increases substantially in a range of 1.95 × 10-5 to 6.0 × 10-3 M (R2 = .9943), with a detection limit of 3.9 × 10-6 M (S/N = 3) and analytical sensitivity of 13.86 mA/M. The biosensor performs well in determining uric acid concentration in human urine samples.