The strategy of precise targeting and <i>in situ</i> oxygenating for enhanced triple-negative breast cancer chemophototherapy

Wu, Manxiang; Chen, Tianxiang; Wang, Lianfu; Akakuru, Ozioma Udochukwu; Ma, Xuehua; Xu, Jing; Hu, Jiapeng; Chen, Jia; Fang, Qianlan; Wu, Aiguo; Li, Qiang

doi:10.1039/d2nr00985d

Cited by 15 publications

(15 citation statements)

References 48 publications

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“…MNMs can be designed to target tumor cells by controlling their sizes and surface modifications. [17,47,83,99,[105][106][107][108][109][110][111] They may induce apoptosis by producing ROS derived from chemo dynamic therapy, which may be further enhanced by exogenous stimuli (light, ultrasound, etc.) (Figure 3a).…”

Section: Cancer Therapymentioning

confidence: 99%

Metal‐Based Nanozymes with Multienzyme‐Like Activities as Therapeutic Candidates: Applications, Mechanisms, and Optimization Strategy

Dai

Xiong

et al. 2022

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manganese(III) oxide (Mn 2 O 3 ), and Prussian blue nanozyme (PBzyme), etc., have multienzyme-like activities, which enable either the efficient production of reactive oxygen species (ROS) to kill tumor cells and bacteria, or the clearance of ROS to reduce oxidative stress and inflammation. [9][10][11][12][13][14] These metal-based nanozymes display multiple antitumor, anti-infective, and anti-inflammatory activities, and offer promise as potential adjuvants, cotreatments, or alternatives to cytotoxic chemotherapeutics, antibiotics, and nonsteroidal anti-inflammatory drugs. [15][16][17] Most nanozymes in preclinical development have single-enzyme-like activity, and are thus limited by insufficient catalytic efficiency, restricted availability of substrate types and concentrations, and activity under single identifiable catalytic conditions. In comparison, those with multienzyme-like activities carry advantages of high catalytic efficiency via amplification or cascade reactions, adaptive responses to dissimilar catalytic conditions, multifunctionality in diverse pathological processes, and capacities to overcome the impediment of insufficient substrates via "self-provision." [18] At present, most reported nanozymes with multienzyme-like activities are metal-based, owing to their unsaturated sites from the inherent structure of metal atoms and the valence changes of the metal centers in case of transition metals. [4] In the last decade, researchers have studied catalytic effects and regulation rules and design schemes of metal-based nanozymes with multienzyme-like activities (MNMs), with goals to remarkably improve their therapeutic efficiency and broaden their range of applications. [15,[19][20][21][22][23][24][25] Previous review articles have discussed the spatial structures and catalytic mechanisms of nanozymes from the perspective of their physical properties, or have summarized the effects of a few types of nanozymes with potential medical applications. [4,6,[26][27][28][29][30][31][32] However, clinical relevance stands as the core motivator of nanozyme research. Therefore, this review concentrates on MNMs. This work focuses on the biological effects of nanozymes based on their intracellular interactions, intending to analyze mechanisms of action and potential therapeutic applications. Herein, we summarize MNMs, their impacts on pathogenesis, underlying mechanisms, potential medical Most nanozymes in development for medical applications only exhibit singleenzyme-like activity, and are thus limited by insufficient catalytic activity and dysfunctionality in complex pathological microenvironments. To overcome the impediments of limited substrate availabilities and concentrations, some metal-based nanozymes may mimic two or more activities of natural enzymes to catalyze cascade reactions or to catalyze multiple substrates simultaneously, thereby amplifying catalysis. Metal-based nanozymes with multienzyme-like activities (MNMs) may adapt to dissimilar catalytic conditions to exert different enzyme-like effects. ...

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Section: Cancer Therapymentioning

confidence: 99%

Metal‐Based Nanozymes with Multienzyme‐Like Activities as Therapeutic Candidates: Applications, Mechanisms, and Optimization Strategy

Dai

Xiong

et al. 2022

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“…Hypoxia is a prominent feature of the tumor microenvironment and has long been considered as a key factor contributing to the tolerance of radiotherapy in solid tumors [35][36][37]. In recent years, researchers have also developed different strategies to alleviate hypoxia within the tumor, such as oxygen delivery to the tumor region [38,39] and in situ oxygen generation [40][41][42] in the tumor region. However, there is a problem with the strategy of delivering oxygen to the hypoxic region in a tumor due to the uneven distribution of blood vessels within the tumor.…”

Section: Introductionmentioning

confidence: 99%

Alleviating the hypoxic tumor microenvironment with MnO2-coated CeO2 nanoplatform for magnetic resonance imaging guided radiotherapy

Deng

Xue

et al. 2023

J Nanobiotechnol

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Background Radiotherapy is a commonly used tool in clinical practice to treat solid tumors. However, due to the unique microenvironment inside the tumor, such as high levels of GSH, overexpressed H2O2 and hypoxia, these factors can seriously affect the effectiveness of radiotherapy. Results Therefore, to further improve the efficiency of radiotherapy, a core–shell nanocomposite CeO2–MnO2 is designed as a novel radiosensitizer that can modulate the tumor microenvironment (TME) and thus improve the efficacy of radiation therapy. CeO2–MnO2 can act as a radiosensitizer to enhance X-ray absorption at the tumor site while triggering the response behavior associated with the tumor microenvironment. According to in vivo and in vitro experiments, the nanoparticles aggravate the killing effect on tumor cells by generating large amounts of ROS and disrupting the redox balance. In this process, the outer layer of MnO2 reacts with GSH and H2O2 in the tumor microenvironment to generate ROS and release oxygen, thus alleviating the hypoxic condition in the tumor area. Meanwhile, the manganese ions produced by degradation can enhance T1-weighted magnetic resonance imaging (MRI). In addition, CeO2–MnO2, due to its high atomic number oxide CeO2, releases a large number of electrons under the effect of radiotherapy, which further reacts with intracellular molecules to produce reactive oxygen species and enhances the killing effect on tumor cells, thus having the effect of radiotherapy sensitization. In conclusion, the nanomaterial CeO2–MnO2, as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystem with radiosensitizing function. Conclusion In conclusion, the nanomaterial CeO2–MnO2, as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystems with radiosensitizing function.

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“…Elleviating hypoxia could be a potential strategy to solve the challenge. Many therapeutic strategies for breast cancer hypoxia were reported including HIF inhibitors [ 12 ], hypoxia-activable prodrug [ 13 ] and in situ oxygenating to modulate TME [ 14 ]. Usually, there two main approaches for normalizing tumor oxygen supply.…”

Section: Introductionmentioning

confidence: 99%

Biomimetic liposomal nanozymes improve breast cancer chemotherapy with enhanced penetration and alleviated hypoxia

Gong

Chen

et al. 2023

J Nanobiotechnol

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Background Doxorubicin (Dox) has been recommended in clinical guidelines for the standard-of-care treatment of breast cancer. However, Dox therapy faces challenges such as hypoxia, acidosis, H2O2-rich conditions and condensed extracellular matrix in TME as well as low targeted ability. Methods We developed a nanosystem H-MnO2-Dox-Col NPs based on mesoporous manganese dioxide (H-MnO2) in which Dox was loaded in the core and collagenase (Col) was wrapped in the surface. Further the H-MnO2-Dox-Col NPs were covered by a fusion membrane (MP) of inflammation-targeted RAW264.7 cell membrane and pH-sensitive liposomes to form biomimetic MP@H-MnO2-Dox-Col for in vitro and in vivo study. Results Our results shows that MP@H-MnO2-Dox-Col can increase the Dox effect with low cardiotoxicity based on multi-functions of effective penetration in tumor tissue, alleviating hypoxia in TME, pH sensitive drug release as well as targeted delivery of Dox. Conclusions This multifunctional biomimetic nanodelivery system exhibited antitumor efficacy in vivo and in vitro, thus having potential for the treatment of breast cancer.

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The strategy of precise targeting and in situ oxygenating for enhanced triple-negative breast cancer chemophototherapy

Abstract: The absence of effective therapeutic targets and tumor hypoxia are the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Biomimetic nanotechnology and tumor microenvironment (TME)-responsiveness bring...

Cited by 15 publications

References 48 publications

Metal‐Based Nanozymes with Multienzyme‐Like Activities as Therapeutic Candidates: Applications, Mechanisms, and Optimization Strategy

Metal‐Based Nanozymes with Multienzyme‐Like Activities as Therapeutic Candidates: Applications, Mechanisms, and Optimization Strategy

Alleviating the hypoxic tumor microenvironment with MnO2-coated CeO2 nanoplatform for magnetic resonance imaging guided radiotherapy

Biomimetic liposomal nanozymes improve breast cancer chemotherapy with enhanced penetration and alleviated hypoxia

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