A Catalase‐Like Metal‐Organic Framework Nanohybrid for O₂‐Evolving Synergistic Chemoradiotherapy

Abstract

Tumor hypoxia, the "Achilles heel" of current cancer therapies,i si ndispensable to drug resistance and poor therapeutic outcomes especially for radiotherapy. Here we propose an in situ catalytic oxygenation strategy in tumor using porphyrinic metal-organic framework (MOF)-gold nanoparticles (AuNPs) nanohybrid as atherapeutic platform to achieve O 2 -evolving chemoradiotherapy. The AuNPs decorated on the surface of MOF effectively stabilize the nanocomposite and serve as radiosensitizers,w hereas the MOF scaffold acts as acontainer to encapsulate chemotherapeutic drug doxorubicin. In vitro and in vivo studies verify that the catalase-like nanohybrid significantly enhances the radiotherapye ffect, alleviating tumor hypoxia and achieving synergistic anticancer efficacy.T his hybrid nanomaterial remarkably suppresses the tumor growth with minimized systemic toxicity,o pening new horizons for the next generation of theranostic nanomedicines.

Metal–Organic Frameworks for Biomedical Applications

“…d) Schematic illustration of the main components of the PEGylated porphyrin Au‐NMOF‐based nanohybrid and the mechanism of O 2 ‐evolving synergistic chemoradiotherapy for tumor treatment. Reproduced with permission 41. Copyright 2019, Wiley‐VCH.…”

“…Recently, Chen and co‐workers fabricated a PEGylated porphyrin Au‐NMOF‐based nanohybrid with biodegradability, stimuli‐responsive O 2 generation, and controllable drug release to achieve O 2 ‐evolving chemoradiotherapy (Figure 5d). 41 Au NPs were grown in situ on the surface of MOFs, which brought about several remarkable advantages, such as increased sensitization of RT, enhanced stability of nanohybrid and alleviated hypoxia during tumor therapy. Afterwards, DOX as anticancer drug was loaded in the MOFs reservoir and combined with Au NPs to form chemoradiotherapy system.…”

“…In this review article, we will summarize the recent developments of MOF‐based composite materials including the synthesis and functionalization8–15 and their biomedical applications in the delivery of cargos including drugs, nucleic acids, proteins, and dyes ( Table 1 ),19,21–23,25–29,31b,d,34–41 bioimaging ( Table 2 ),43–45,47–54 antimicrobial ( Table 3 ),57,60–67 biosensing ( Table 4 ),69–73,75–86 and biocatalysis ( Table 5 ). 91–95 Moreover, the potential of MOFs for biomedical applications has been clarified through the analysis of recent examples reported in literature.…”

Cu2MoS4/Au Heterostructures with Enhanced Catalase‐Like Activity and Photoconversion Efficiency for Primary/Metastatic Tumors Eradication by Phototherapy‐Induced Immunotherapy

“…Tumor hypoxia, which is an inherent feature in solid tumors, readily leads to cancer proliferation and metastasis, and severely restrict O 2 ‐dependent PDT effect. [ 54,55 ] Notably, the hypoxia condition could be alleviated effectively via decomposing over‐expressed H 2 O 2 into O 2 in TME by catalase. Based on the CAT‐like activity of CMS and CMS/Au, the O 2 ‐evolving performance in vitro and in vivo was studied further.…”

Designing Hypoxia‐Responsive Nanotheranostic Agents for Tumor Imaging and Therapy

“…This smart design was shown to achieve a highly accurate and effective PDT in oxygen‐deprived tumor tissue and reduce side effects on normal tissues. Using the same strategy, Chen and co‐workers [ 98 ] developed DOX@MOF‐Au‐PEG hybrid nanoparticles by decorating the surface with Au NPs and encapsulating DOX inside the pore (Figure 17c). Au NPs possess an intrinsic catalase‐like ability to decompose H 2 O 2 into oxygen, thus abrogating the antidrug properties of the hypoxic tumor.…”