Highly Stable Silica-Coated Bismuth Nanoparticles Deliver Tumor Microenvironment-Responsive Prodrugs to Enhance Tumor-Specific Photoradiotherapy

Abstract

Radiosensitizers are agents capable of amplifying injury to tumor tissues by enhancing DNA damage and fortifying production of radical oxygen species (ROS). The use of such radiosensitizers in the clinic, however, remains limited by an insufficient ability to differentiate between cancer and normal cells and by the presence of a reversible glutathione system that can diminish the amount of ROS generated. Here, to address these limitations, we design an H2O2-responsive prodrug which can be premixed with lauric acid (melting point ∼43 °C) and loaded around the surface of silica-coated bismuth nanoparticles (BSNPs) for cancer-specific photoradiotherapy. Particularly, silica coating confers BSNPs with improved chemical stability against both near-infrared light and X-rays. Upon photothermal heating, lauric acid is melted to trigger prodrug release, followed by its transformation into p-quinone methide via H2O2 stimulation to irreversibly alkylate glutathione. Concurrently, this heat boosts tumor oxygenation and helps relieve the hypoxic microenvironment. Following sequential irradiation by X-rays, BSNPs generate plentiful ROS, which act in combination with these events to synergistically induce cell death via DNA breakage and mitochondria-mediated apoptosis pathways, ultimately enabling effective inhibition of tumor growth in vivo with high tumor specificity and reduced side effects. Collectively, this work presents a promising approach for the improvement of other ROS-responsive proalkylating agents, while simultaneously highlighting a robust nanosystem for combining these prodrugs with photoradiosensitizers to realize precision photoradiotherapy.

An Ultrasmall Fe3O4‐Decorated Polydopamine Hybrid Nanozyme Enables Continuous Conversion of Oxygen into Toxic Hydroxyl Radical via GSH‐Depleted Cascade Redox Reactions for Intensive Wound Disinfection

“…In addition, compared with PDA/Fe 3 O 4 (Fresh), the PDA/Fe 3 O 4 (Ox) exhibited stronger property for GSH depletion, which was probably due to the existence of more quinone groups in PDA/Fe 3 O 4 (Ox). [ 59,60,62 ] Interestingly, we found that the GSH‐depleting property of PDA/Fe 3 O 4 could be regenerated by a simple O 2 ‐mediated oxidization and had no obvious decrease after four redox cycles (Figure 3G). Furthermore, we also compared the effects of different components of PDA/Fe 3 O 4 nanozymes on the GSH depletion.…”

Metal–Organic Frameworks Nanoarchitectures Boost Catalytic Activity for the Construction of Sensitive Immunosensor

“…Furthermore, the catalytic activity of HRP@NSMOFs is confirmed by monitoring the hydroxyl radical yield through the oxidation mechanism of terephthalic acid. [51,52] As illustrated in Figure 3f, HRP@NSMOFs possess the highest fluorescence enhancement of ≈160%, meaning that and c) nitrogen adsorption isotherms of HRP@MOFs with different dosages of PLGA and pure MOFs, respectively. d) The pore size analysis of HRP@TMOFs, HRP@NSMOFs and HRP@FMOFs, respectively.…”

Industrialization’s eye view on theranostic nanomedicine

“…Xiang et al fabricated silica-coated bismuth NPs covered with lauric acid that contained a prodrug (BSBCL) for radiophotothermal therapy (Xiang et al, 2021). The Si coating imparted hydrolytic stability and photothermal and Frontiers in Chemistry frontiersin.org radiosensitizing properties of the Bi NPs, while the lauric acid acted as a temperature-sensitive gatekeeper.…”