Hypoxic tumor therapy based on free radicals

Zheng, Jingtao; Pan, Yuchen; Chen, Yubin; Li, Junyan; Li, Weishuo

doi:10.1039/d3qm00206c

Mater. Chem. Front.

2023

DOI: 10.1039/d3qm00206c

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Hypoxic tumor therapy based on free radicals

Jingtao Zheng

Yuchen Pan

Yubin Chen

et al.

Abstract: Hypoxia is an intrinsic characteristic of many malignant solid tumors, contributing largely to tumor progression and metastasis, as well as resistance to most standard therapeutic modalities, such as radiotherapy, chemotherapy....

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Cited by 4 publications

References 152 publications

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Quintuple Free‐Radical Therapy: An Ultralong‐Retention FAND for NIR‐Involved Multiple Site‐Acting Hypoxic Tumor Therapy

Zhang,

Zhao,

Fang

et al. 2024

Adv Funct Materials

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The heavy dependence on intratumoral O2 and H2O2 availability has greatly restricted ROS‐based therapy. Although O2/H2O2‐irrelevant free‐radical nanogenerator has garnered tremendous attention as a promising anticancer candidate to overcome the above intrinsic limitations of ROS‐based treatment, the practical therapeutic efficacy of free‐radical therapy is still hindered by limited free‐radical type and inferior tumor retention performance. Herein, inspired by the new concept of full‐API nanodrug (FAND) with 100% active pharmaceutical ingredient (API) content and repurposing of clinical anti‐malaria drug artesunate (ARTE) as an anticancer free‐radical generator, the AFeI FANDs composed of ARTE, human essential Fe3+, and FDA‐approved fluorescent agent ICG for hypoxic tumor therapy are rationally designed and constructed. Attractively, the completely pharmaceutically active components ARTE, Fe3+, and ICG can be responsively liberated in the acidic tumor microenvironment and synergistically produce five types of free radicals including •O2−, •C, •OH, LOO•, and 1O2, leading to robust mitochondrial injury, nuclear DNA damage, and lipid peroxides. More importantly, the AFeI FANDs displayed ultralong tumor retention longer than 108 h and favorable tumor suppression outcomes under mild NIR irradiation. Collectively, the presented first paradigm of FAND‐based quintuple free‐radical therapy expands new horizons for the development of clinically transferable nanomedicine for tumor therapy.

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Quintuple Free‐Radical Therapy: An Ultralong‐Retention FAND for NIR‐Involved Multiple Site‐Acting Hypoxic Tumor Therapy

Zhang,

Zhao,

Fang

et al. 2024

Adv Funct Materials

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Custom‐Design of Multi‐Stimuli‐Responsive Degradable Silica Nanoparticles for Advanced Cancer‐Specific Chemotherapy

Zhang,

Zhou,

Tang

et al. 2024

Small

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Chemotherapy is crucial in oncology for combating malignant tumors but often encounters obatacles such as severe adverse effects, drug resistance, and biocompatibility issues. The advantages of degradable silica nanoparticles in tumor diagnosis and treatment lie in their ability to target drug delivery, minimizing toxicity to normal tissues while enhancing therapeutic efficacy. Moreover, their responsiveness to both endogenous and exogenous stimuli opens up new possibilities for integrating multiple treatment modalities. This review scrutinizes the burgeoning utility of degradable silica nanoparticles in combination with chemotherapy and other treatment modalities. Commencing the elucidation of degradable silica synthesis and degradation mechanisms, emphasis is placed on the responsiveness of these materials to endogenous (e.g., pH, redox reactions, hypoxia, and enzymes) and exogenous stimuli (e.g., light and high‐intensity focused ultrasound). Moreover, this exploration delves into strategies harnessing degradable silica nanoparticles in chemotherapy alone, coupled with radiotherapy, photothermal therapy, photodynamic therapy, gas therapy, immunotherapy, starvation therapy, and chemodynamic therapy, elucidating multimodal synergies. Concluding with an assessment of advances, challenges, and constraints in oncology, despite hurdles, future investigations are anticipated to augment the role of degradable silica in cancer therapy. These insights can serve as a compass for devising more efficacious combined tumor treatment strategies.

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Empowering radiotherapy: Harnessing nanomedicines to enhance radiation response and boost antitumor efficacy

Zhuo,

Aishajiang,

Liang

et al. 2024

Coordination Chemistry Reviews

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Hypoxic tumor therapy based on free radicals

Abstract: Hypoxia is an intrinsic characteristic of many malignant solid tumors, contributing largely to tumor progression and metastasis, as well as resistance to most standard therapeutic modalities, such as radiotherapy, chemotherapy....

Cited by 4 publications

References 152 publications

Quintuple Free‐Radical Therapy: An Ultralong‐Retention FAND for NIR‐Involved Multiple Site‐Acting Hypoxic Tumor Therapy

Quintuple Free‐Radical Therapy: An Ultralong‐Retention FAND for NIR‐Involved Multiple Site‐Acting Hypoxic Tumor Therapy

Custom‐Design of Multi‐Stimuli‐Responsive Degradable Silica Nanoparticles for Advanced Cancer‐Specific Chemotherapy

Empowering radiotherapy: Harnessing nanomedicines to enhance radiation response and boost antitumor efficacy

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