Intelligent Pd_1.7Bi@CeO₂ Nanosystem with Dual-Enzyme-Mimetic Activities for Cancer Hypoxia Relief and Synergistic Photothermal/Photodynamic/Chemodynamic Therapy

Abstract

Reactive oxygen species-mediated therapeutic strategies, including chemodynamic therapy (CDT) and photodynamic therapy (PDT), have exhibited translational promise for effective cancer management. However, monotherapy often ends up with the incomplete elimination of the entire tumor due to inherent limitations. Herein, we report a core–shell-structured Pd1.7Bi@CeO2-ICG (PBCI) nanoplatform constructed by a facile and effective strategy for synergistic CDT, PDT, and photothermal therapy. In the system, both Pd1.7Bi and CeO2 constituents exhibit peroxidase- and catalase-like characteristics, which not only generate cytotoxic hydroxyl radicals (•OH) for CDT but also produce O2 in situ and relieve tumor hypoxia for enhanced PDT. Furthermore, upon 808 nm laser irradiation, Pd1.7Bi@CeO2 and indocyanine green (ICG) coordinately prompt favorable photothermia, resulting in thermodynamically amplified catalytic activities. Meanwhile, PBCI is a contrast agent for near-infrared fluorescence imaging to determine the optimal laser therapeutic window in vivo. Consequently, effective tumor elimination was realized through the above-combined functions. The as-synthesized unitary PBCI theranostic nanoplatform represents a potential one-size-fits-all approach in multimodal synergistic therapy of hypoxic tumors.

In Vitro Synergistic Photodynamic, Photothermal, Chemodynamic, and Starvation Therapy Performance of Chlorin e6 Immobilized, Polydopamine-Coated Hollow, Porous Ceria-Based, Hypoxia-Tolerant Nanozymes Carrying a Cascade System

“…Here, the fluorescence intensity also increased with the increasing concentration of H-CeO 2 @PDA@GOx NPs, which indicates the formation of additional 2-HTPA likely due to the generation of more · OH in the presence of larger amount of H-CeO 2 @PDA@GOx NPs. ,, Hence, both the POD-like activity and the fluorescence assay clearly demonstrate the · OH radical generation ability of H-CeO 2 @PDA@GOx NPs in the presence of glucose (Figure C,D). The conversion of nontoxic glucose to the · OH radical which is highly toxic for the tumor microenvironment demonstrates the CDT function of H-CeO 2 @PDA@GOx NPs originating from their Fenton-like activity. ,, Note that highly toxic · OH radical production ability and its evaluation for CDT have been demonstrated using various CeO 2 -based STAs against different tumor cells. ,− ,,,, …”

“…The CAT-like activity of these NPs led to the decomposition of the H 2 O 2 , which was generated by the oxidation of glucose, into O 2 for hypoxia relief within the tumor microenvironment. H 2 O 2 was further consumed by the cytotoxic · OH radicals produced via the Fenton-like activity of H-CeO 2 NPs that mediate for simultaneous application of CDT with ST. ,,,, An appreciable improvement in the effectiveness of PDT was observed by O 2 generation initiated by decomposition of glucose via the cascade nanozyme/enzyme system. The effectiveness of ST and CDT was markedly enhanced by the temperature elevation induced by photothermal conversion ability of H-CeO 2 @Ce6@PDA@GOx NPs.…”

“…For instance, HA/ICG-loaded CeO 2 NPs were evaluated for PTT/PDT by alleviating hypoxia with MCF-7 cells . Pd1.7 Bi@CeO 2 NSs loaded with ICG were used for PTT/PDT and CDT using 4T1 cells with hypoxia relief . A Ce6 and BSA-loaded CeO 2 /UCNP composite was synthesized for PDT with hypoxia relief on ID8 cells .…”

H2O2 Self-Supply and Glutathione Depletion Engineering Nanoassemblies for NIR-II Photoacoustic Imaging of Tumor Tissues and Photothermal-Enhanced Gas Starvation-Primed Chemodynamic Therapy

“…The GOx can catalyze the redox reaction of glucose to produce a large amount of H 2 O 2 , which results in depletion of glucose. Free Cu + reacts with H 2 O 2 like in the Fenton reaction to generate • OH (Figure b), thereby activating starvation therapy and CDT . To demonstrate the feasibility of this mechanism, we used absorption spectroscopy and paramagnetic electron spin resonance (ESR) spectroscopy, with 3,3,5,5-tetramethylbienzidine (TMB) as the indicator and 5,5-dimethyl-1-pyrroline-oxide (DMPO) as the capture agent to evaluate the generation process of • OH in the cascade reaction described above.…”

Defect-rich sonosensitizers based on CeO2 with Schottky heterojunctions for boosting sonodynamic/chemodynamic synergistic therapy

“…CeO 2 exhibited great potential for cancer therapy. 21,22 First, CeO 2 is a typical N-type semiconductor, which confers it potential as a sonosensitizer. 23 Moreover, CeO 2 is prone to generating oxygen defects by doping a metal ion or an anion, further improving the treatment effect of SDT by inhibiting electron–hole recombination.…”