RESUMEN
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.
Asunto(s)
Profármacos , Profármacos/farmacología , Transferencia de Energía , Especies Reactivas de Oxígeno , Inmunoterapia , Línea Celular TumoralRESUMEN
Despite DNA nanotechnology has spawned a broad variety and taken a giant leap toward cancer theranostic applications over the last decade, the homogeneous DNA nanostructures often suffer from fatal degradation due to their limited stability and specificity. Herein, for the first time, we report a stable DNA tetrahedra-gold nanoclusters (DT/AuNCs) nanohybrid with a self-assembly/programmed disassembly manner for stimuli-responsive tumor imaging and gene-chemo therapy. By utilizing the multifunctional peptides with positive and legumain-specific domains as bioligands, AuNCs were synthesized as signal generators and gate guard attached on the dual-responsive DT, forming the DT/AuNCs with sequential response to legumain-TK1 mRNA & glutathione. The tumorous biomarker of legumain initiated the signal generation relying on the nanosurface energy transfer effect of AuNCs and denudation of DT-Dox (preliminary disassembly). Successively, the dual-responsive DT-Dox administrated a sequential fragmentation along with Dox release in response to the up-regulated glutathione and TK1 mRNA (secondary disassembly), thereby leading to combined gene silencing and chemo-therapy. The results revealed that the DT/AuNCs nanohybrids significantly improved the stability and enhanced the therapeutic efficiency compared to naked DT. Endowing with remarkable stability against biological milieu and site specificity for drug release, our work exhibits a new prospect of fabricating DNA-based nanohybrids for precise tumor theranostics.
Asunto(s)
Nanopartículas del Metal , Neoplasias , ADN/química , Glutatión , Oro/química , Nanopartículas del Metal/química , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , ARN Mensajero/químicaRESUMEN
Herein, Fe3O4 NP@ZIF-8/MoS2 QD-based electrochemiluminescence (ECL) biosensor with nanosurface energy transfer strategy was successfully developed for point-of-care determination of ATP. With the porous structure and poor electron transfer ability, Fe3O4 NP@ZIF-8 complex was first used as an excellent catalyst in ECL. The complex catalyzed the coreactant for more free radicals and hindered the quenching effect of Fe3O4 nanoparticles (NPs) on quantum dots (QDs). In ECL-nanosurface energy transfer (NSET) system, through the specific binding of complementary DNA linked to MoS2 QDs (QDs-cDNA) and aptamer linked to Au NPs, interaction between the point dipole of MoS2 QDs and the collective dipoles of Au NPs quenched ECL signal. When ATP was captured by aptamer, the ECL-NSET system was taken apart, which resulted in the recovery of ECL signal. Moreover, changes of the ECL imaging can be captured by a smartphone, which enabled point-of-care determination of ATP from 0.05 nmol L-1 to 200 nmol L-1 with LOD of 0.015 nmol L-1. With superior specificity and stability, the sensing system showed significant potential about the application of catalysts coated with ZIF and NSET in point-of-care ECL determination.
Asunto(s)
Técnicas Biosensibles , Puntos Cuánticos , Adenosina Trifosfato , Técnicas Electroquímicas , Transferencia de Energía , Mediciones Luminiscentes , Molibdeno , Sistemas de Atención de PuntoRESUMEN
OBJECTIVES: To prepare fluorescent carbon dots for loading cationic anticancer drug through donor-quenched nanosurface energy transfer in visible sensing of drug release. RESULTS: Highly fluorescent carbon dots (CDs) were prepared by a facile hydrothermal approach from citric acid and o-phenylenediamine. The obtained CDs showed a high quantum yield of 46 % and exhibited good cytocompatibility even at 1 mg/ml. The cationic anticancer drug doxorubicin (DOX) can be loaded onto the negatively charged CDs through electrostatic interactions. Additionally, the fluorescent CDs feature reversible donor-quenched mode nanosurface energy transfer. When loading the energy receptor DOX, the donor CDs' fluorescence was switched "off", while it turned "on" again after DOX release from the surface through endocytic uptake. CONCLUSIONS: Most DOX molecules were released from the CDs after 6 h incubation and entered cell nuclear region after 8 h, suggesting the drug delivery system may have potential for visible sensing in drug release.