Mito‐Bomb: Targeting Mitochondria for Cancer Therapy

Guo, Xiaolu; Yang, Naidi; Ji, Wenhui; Zhang, Hang; Dong, Xiao; Zhou, Zhiqiang; Li, Lin; Shen, Han‐Ming; Yao, Shao Q.; Huang, Wei

doi:10.1002/adma.202007778

Cited by 188 publications

(138 citation statements)

References 392 publications

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“…So far, regulating the function of mitochondria in cancer cells to control the level of intracellular ROS has already been developed as a powerful anti-cancer method [ 94 , 95 ]. Compared with normal cells, the mitochondria of cancer cells always have a higher membrane potential [ 96 ], and the delivery of inorganic drugs into mitochondria based on the higher mitochondrial membrane potential allows selective targeting of cancer cell mitochondria to kill cancer cells [ 97 , 98 ]. Recently, anti-cancer metal complexes targeting mitochondria have drawn strong interest because of their strong anti-cancer activities, limited side effects, and versatile photophysical properties.…”

Section: Anti-cancer Metal Complexes Activating Ros-mediated Signaling From Mitochondriamentioning

confidence: 99%

Metal Complexes or Chelators with ROS Regulation Capacity: Promising Candidates for Cancer Treatment

Wang

et al. 2021

Molecules

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Reactive oxygen species (ROS) are rapidly eliminated and reproduced in organisms, and they always play important roles in various biological functions and abnormal pathological processes. Evaluated ROS have frequently been observed in various cancers to activate multiple pro-tumorigenic signaling pathways and induce the survival and proliferation of cancer cells. Hydrogen peroxide (H2O2) and superoxide anion (O2•−) are the most important redox signaling agents in cancer cells, the homeostasis of which is maintained by dozens of growth factors, cytokines, and antioxidant enzymes. Therefore, antioxidant enzymes tend to have higher activity levels to maintain the homeostasis of ROS in cancer cells. Effective intervention in the ROS homeostasis of cancer cells by chelating agents or metal complexes has already developed into an important anti-cancer strategy. We can inhibit the activity of antioxidant enzymes using chelators or metal complexes; on the other hand, we can also use metal complexes to directly regulate the level of ROS in cancer cells via mitochondria. In this review, metal complexes or chelators with ROS regulation capacity and with anti-cancer applications are collectively and comprehensively analyzed, which is beneficial for the development of the next generation of inorganic anti-cancer drugs based on ROS regulation. We expect that this review will provide a new perspective to develop novel inorganic reagents for killing cancer cells and, further, as candidates or clinical drugs.

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Section: Anti-cancer Metal Complexes Activating Ros-mediated Signaling From Mitochondriamentioning

confidence: 99%

Metal Complexes or Chelators with ROS Regulation Capacity: Promising Candidates for Cancer Treatment

Wang

et al. 2021

Molecules

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“…This endeavor has been promoted by the establishment of several important concepts including the peptide amphiphiles (Lowik and van Hest, 2004;Cui et al, 2010), the enzyme-instructed self-assembly (EISA) (Zhou and Xu, 2015;He et al, 2020c), and the in vivo self-assembly (Zhang et al, 2015;He P.-P. et al, 2020;Mamuti et al, 2021). Since mitochondria serve as a potential target for cancers (Guo et al, 2021;Liew et al, 2021), dozens of mitochondria-targeted selfassembled peptide-nanomaterials have been reported (Table 1), including the pre-assembled peptide-nanomaterials that locate mitochondria and in situ self-assembling peptides that assemble in mitochondria. In this section, we discuss the former.…”

Section: Self-assembling Peptidementioning

confidence: 99%

Mitochondria-Targeted Self-Assembly of Peptide-Based Nanomaterials

Luo

Gao

Duan

et al. 2021

Front. Bioeng. Biotechnol.

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Mitochondria are well known to serve as the powerhouse for cells and also the initiator for some vital signaling pathways. A variety of diseases are discovered to be associated with the abnormalities of mitochondria, including cancers. Thus, targeting mitochondria and their metabolisms are recognized to be promising for cancer therapy. In recent years, great efforts have been devoted to developing mitochondria-targeted pharmaceuticals, including small molecular drugs, peptides, proteins, and genes, with several molecular drugs and peptides enrolled in clinical trials. Along with the advances of nanotechnology, self-assembled peptide-nanomaterials that integrate the biomarker-targeting, stimuli-response, self-assembly, and therapeutic effect, have been attracted increasing interest in the fields of biotechnology and nanomedicine. Particularly, in situ mitochondria-targeted self-assembling peptides that can assemble on the surface or inside mitochondria have opened another dimension for the mitochondria-targeted cancer therapy. Here, we highlight the recent progress of mitochondria-targeted peptide-nanomaterials, especially those in situ self-assembly systems in mitochondria, and their applications in cancer treatments.

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“…ROS has strong oxidative activity and can cause severe oxidative damage ( Qin et al, 2021 ). Therefore, it is an extremely efficient strategy to promote mitochondrial damage to kill cancer cells by increasing the level of ROS in the mitochondrial region ( Guo et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Mitochondria-Targeting Chemodynamic Therapy Nanodrugs for Cancer Treatment

Chen

Wang

et al. 2022

Front. Pharmacol.

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Mitochondria, as one of the most critical subcellular organelles of cancer cells, are very vulnerable and often on the verge of oxidative stress. The classic chemodynamic therapy (CDT) directly employs endogenous chemical energy to trigger reactive oxygen species (ROS) burst and destroy tumor cells. However, the effectiveness of CDT is restricted by the limited diffusion distance and short half-life of ROS. From this perspective, the treatment method (mitochondria-targeting chemodynamic therapy nanodrugs, M-CDT nanodrugs) that can generate high levels of ROS at the mitochondrial site is extremely efficient and promising for cancer treatment. Currently, many emerging M-CDT nanodrugs have been demonstrated excellent spatial specificity and anti-cancer efficacy. In this minireview, we review various proof-of-concept researches based on different M-CDT nanodrugs designs to overcome the limits of the efficacy of CDT, mainly divided into four strategies: supplying H2O2, non-H2O2 dependent CDT, eliminating GSH and enhancing by hyperthermia therapy (HT). These well-designed M-CDT nanodrugs greatly increase the efficacy of CDT. Finally, the progress and potential of M-CDT nanodrugs are discussed, as well as their limitations and opportunities.

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Mito‐Bomb: Targeting Mitochondria for Cancer Therapy

Cited by 188 publications

References 392 publications

Metal Complexes or Chelators with ROS Regulation Capacity: Promising Candidates for Cancer Treatment

Metal Complexes or Chelators with ROS Regulation Capacity: Promising Candidates for Cancer Treatment

Mitochondria-Targeted Self-Assembly of Peptide-Based Nanomaterials

Mitochondria-Targeting Chemodynamic Therapy Nanodrugs for Cancer Treatment

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