Strategies of Alleviating Tumor Hypoxia and Enhancing Tumor Therapeutic Effect by Macromolecular Nanomaterials

Jin, Zhenyu; Zhao, Qingyu; Yuan, Shanmei; Jiang, Wei; Hu, Yong

doi:10.1002/mabi.202100092

Cited by 14 publications

(14 citation statements)

References 93 publications

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“…PFCs demonstrated an outstanding oxygen affinity due to their fluorine atoms in the carbon skeleton ( 21 ). Of the high biocompatibility and chemical stability, PFCs have been widely used in the clinic, such as in organ transplantation and ultrasound imaging.…”

Section: Physical Strategiesmentioning

confidence: 99%

Oxygen switches: Refueling for cancer radiotherapy

Wang²,

Li³

et al. 2023

Front. Oncol.

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Radiotherapy remains the major therapeutic intervention for tumor patients. However, the hypoxic tumor microenvironment leads to treatment resistance. Recently, a burgeoning number of nano-radiosensitizers designed to increase the oxygen concentration in tumors were reported. These nano radiosensitizers served as oxygen carriers, oxygen generators, and even sustained oxygen pumps, attracting increased research interest. In this review, we focus on the novel oxygen-enrich nano radiosensitizers, which we call oxygen switches, and highlight their influence in radiotherapy through different strategies. Physical strategies-based oxygen switches carried O2 into the tumor via their high oxygen capacity. The chemical reactions to generate O2in situ were triggered by chemical strategies-based oxygen switches. Biological strategies-based oxygen switches regulated tumor metabolism, remodeled tumor vasculature, and even introduced microorganisms-mediated photosynthesis for long-lasting hypoxia alleviating. Moreover, the challenges and perspectives of oxygen switches-mediated oxygen-enrich radiotherapy were discussed.

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Section: Physical Strategiesmentioning

confidence: 99%

Oxygen switches: Refueling for cancer radiotherapy

Wang²,

Li³

et al. 2023

Front. Oncol.

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“…Methods suggested to restore the tumor oxygen supply before or during radiotherapy include erythrocyte transfusion, erythropoietin administration, and hyperbaric oxygen (HBO) treatment, among others. To date, compelling evidence has demonstrated that hypoxia can be successfully overcome with the use of relevant nanomaterials, as also summarized by several excellent reviews[ 241 - 243 ]. For instance, some simulated oxygen- or water-soluble components can be employed to improve the effect of radiotherapy.…”

Section: Application Of Nanotechnology In Conquering Therapeutic Resi...mentioning

confidence: 99%

Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer

Ren¹,

Zhang²,

Guo³

et al. 2023

World J Gastroenterol

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Colorectal cancer (CRC) is the most common digestive malignancy across the world. Its first-line treatments applied in the routine clinical setting include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, resistance to therapy has been identified as the major clinical challenge that fails the treatment method, leading to recurrence and distant metastasis. An increasing number of studies have been attempting to explore the underlying mechanisms of the resistance of CRC cells to different therapies, which can be summarized into two aspects: (1) The intrinsic characters and adapted alterations of CRC cells before and during treatment that regulate the drug metabolism, drug transport, drug target, and the activation of signaling pathways; and (2) the suppressive features of the tumor microenvironment (TME). To combat the issue of therapeutic resistance, effective strategies are warranted with a focus on the restoration of CRC cells’ sensitivity to specific treatments as well as reprogramming impressive TME into stimulatory conditions. To date, nanotechnology seems promising with scope for improvement of drug mobility, treatment efficacy, and reduction of systemic toxicity. The instinctive advantages offered by nanomaterials enable the diversity of loading cargoes to increase drug concentration and targeting specificity, as well as offer a platform for trying the combination of different treatments to eventually prevent tumor recurrence, metastasis, and reversion of therapy resistance. The present review intends to summarize the known mechanisms of CRC resistance to chemotherapy, radiotherapy, immunotherapy, and targeted therapy, as well as the process of metastasis. We have also emphasized the recent application of nanomaterials in combating therapeutic resistance and preventing metastasis either by combining with other treatment approaches or alone. In summary, nanomedicine is an emerging technology with potential for CRC treatment; hence, efforts should be devoted to targeting cancer cells for the restoration of therapeutic sensitivity as well as reprogramming the TME. It is believed that the combined strategy will be beneficial to achieve synergistic outcomes contributing to control and management of CRC in the future.

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“…Glucose oxidase (GOD) is a good choice to enhance H 2 O 2 and to lower pH by oxidizing glucose into H 2 O 2 and gluconic acid. , According to the Warburg effect, tumor cells are more dependent on nutrients, such as glucose, than normal cells, and glucose plays a key role in promoting the metabolism of tumor cells. ,, Therefore, GOD-mediated glucose metabolism cannot only accelerate Fenton/Fenton-like reactions but also the starvation of tumors for starvation therapy. , However, one of the necessary conditions for GOD to oxidize glucose is O 2 , and the concentration of O 2 in most solid tumor tissues is noticeably lower than that in normal tissues. , Unfortunately, O 2 depletion caused by GOD can further exacerbate the hypoxic microenvironment . A convenient and effective strategy to overcome hypoxia has recently been introduced by generating O 2 in situ instead of transporting it, where high H 2 O 2 levels in the TME can self-produce O 2 by loading enzymes, inorganic nanocomposites, or metal oxides. − For instance, catalase-mimicking platinum nanoparticles (Pt NPs) have been widely used in the construction of nanomaterials as a low-cost alternative to natural enzymes, which can decrease tumor hypoxia by catalyzing H 2 O 2 production of O 2 in situ. , Of special note is that sufficient H 2 O 2 can be generated during the oxidation of glucose by GOD to promote Fenton-like reactions .…”

Section: Introductionmentioning

confidence: 99%

Metal–Organic Framework PCN-224 Integrated with Manganese Dioxide, Platinum Nanoparticles, and Glucose Oxidase for Enhanced Cancer Chemodynamic Therapy

Zhu

Gui

Song

et al. 2023

ACS Appl. Nano Mater.

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Chemodynamic therapy (CDT) is a highly promising tumor treatment modality that uses the Fenton reaction to convert intracellular hydrogen peroxide (H2O2) into cytotoxic hydroxyl groups (•OH). However, the therapeutic effects of CDT have been restricted by weak acidic pH values, insufficient H2O2 levels, and high glutathione (GSH) concentrations in the tumor microenvironment (TME). In this study, to construct PCN-224-Pt/GOD, porphyrin-based metal–organic framework nanoparticles (PCN-224) were used as the carrier to load Pt and glucose oxidase (GOD). The surface of PCN-224-Pt/GOD was covered with manganese dioxide (MnO2) to fabricate the multifunctional composite nanoparticles PCN-224-Pt/GOD@MnO2 (P–P/GOD@Mn). P–P/GOD@Mn was used to increase H2O2 levels and to decrease GSH levels for combined CDT and starvation therapy. As a result, we developed P–P/GOD@Mn nanoparticles (diameter, approximately 280 nm) with favorable size and biocompatibility. Under simulated TME conditions, P–P/GOD@Mn nanoparticles could catalyze H2O2 to generate cytotoxic hydroxyl radicals (•OH), consume glutathione (GSH), and decompose H2O2 to generate oxygen (O2). Cellular toxicity assay results showed that P–P/GOD@Mn killed MCF-7 cells in the TME, with a rate of 77%. The results of tumor-bearing mouse experiments proved that P–P/GOD@Mn nanoparticles could significantly suppress tumor cell growth, which shows the great potential of this entity in CDT and its possibility in bimodal cancer therapy.

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Strategies of Alleviating Tumor Hypoxia and Enhancing Tumor Therapeutic Effect by Macromolecular Nanomaterials

Cited by 14 publications

References 93 publications

Oxygen switches: Refueling for cancer radiotherapy

Oxygen switches: Refueling for cancer radiotherapy

Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer

Metal–Organic Framework PCN-224 Integrated with Manganese Dioxide, Platinum Nanoparticles, and Glucose Oxidase for Enhanced Cancer Chemodynamic Therapy

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