Calcium-chelated nanosystem reversing cancer chemoresistance via replenishing intracellular calcium ions

Wang, Chenglong; Xu, Xiaolin; Xiong, Shuhan; Zhang, Peipei; Yuan, Jia; Gao, Xuzhu; Guan, Wencai; Wang, Fanchen; Li, Xin; Leng, Tao; Dou, Hongjing; Xu, Guoxiong

doi:10.1016/j.cej.2022.137500

Cited by 9 publications

(7 citation statements)

References 36 publications

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“…As a second messenger in cell signaling, calcium ions have many physiological functions, including muscle contraction, neuronal excitation, cell migration and growth, and cell death. [130][131][132] Therefore, the role of calcium ions in tumor treatment has gradually entered the vision of scientists. However, the application of calcium-ion-involved therapy is often limited by the dose-dependent toxicity, short cycle times, low calcium ion release, poor specific ability, and undesirable tumor therapeutic effect.…”

Section: Cu-nanostructure-initiated Combination Therapy Of Cdt With C...mentioning

confidence: 99%

Multifaceted Roles of Copper Ions in Anticancer Nanomedicine

Yang

Song

et al. 2023

Adv Healthcare Materials

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The significantly increased copper level in tumor tissues and serum indicates the close association of copper ions with tumor development, making copper ions attractive targets in the development of novel tumor treatment methods. The advanced nanotechnology developed in the past decades provides great potential for tumor therapy, among which Cu‐based nanotherapeutic systems have received greater attention. Here, the multifaceted roles of copper ions in cancer progression are summarized and the recent advances in the copper‐based nanostructures or nanomedicines for different kinds of tumor therapies including copper depletion therapy, copper‐based cytotoxins, copper‐ion‐based chemodynamic therapy and its combination with other treatments, and copper‐ion‐induced ferroptosis and cuproptosis activation are discussed. Furthermore, the perspectives for the further development of copper‐ion‐based nanomedicines for tumor therapy and clinic translation are presented by the authors.

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Section: Cu-nanostructure-initiated Combination Therapy Of Cdt With C...mentioning

confidence: 99%

Multifaceted Roles of Copper Ions in Anticancer Nanomedicine

Yang

Song

et al. 2023

Adv Healthcare Materials

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“…Intrinsic or acquired chemoresistance is a major hurdle in successful cancer treatment as it often leads to cancer relapse and metastasis, which, in turn, reduces the efficacy of cancer treatment and causes patient death. This resistance can arise either to a single anti-cancer drug or to multiple anti-cancer drugs that differ structurally and/or functionally [ 6 , 7 ] . This is due to underlying genetic mutations, tumour heterogeneity, activated intrinsic pathways, pharmacological factors, and the tumour microenvironment (TME) [ 3 , 7 , 8 ] .…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of calcium homeostasis in cancer and its role in chemoresistance

Kumari,

Pullaguri,

Rath

et al. 2024

Cancer Drug Resist

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Globally, cancer, as a major public health concern, poses a severe threat to people’s well-being. Advanced and specialized therapies can now cure the majority of people with early-stage cancer. However, emerging resistance to traditional and novel chemotherapeutic drugs remains a serious issue in clinical medicine. Chemoresistance often leads to cancer recurrence, metastasis, and increased mortality, accounting for 90% of chemotherapy failures. Thus, it is important to understand the molecular mechanisms of chemoresistance and find novel therapeutic approaches for cancer treatment. Among the several factors responsible for chemoresistance, calcium (Ca2+) dysregulation plays a significant role in cancer progression and chemoresistance. Therefore, targeting this derailed Ca2+ signalling for cancer therapy has become an emerging research area. Of note, the Ca2+ signal and its proteins are a multifaceted and potent tool by which cells achieve specific outcomes. Depending on cell survival needs, Ca2+ is either upregulated or downregulated in both chemosensitive and chemoresistant cancer cells. Consequently, the appropriate treatment should be selected based on Ca2+ signalling dysregulation. This review discusses the role of Ca2+ in cancer cells and the targeting of Ca2+ channels, pumps, and exchangers. Furthermore, we have emphasised the role of Ca2+ in chemoresistance and therapeutic strategies. In conclusion, targeting Ca2+ signalling is a multifaceted process. Methods such as site-specific drug delivery, target-based drug-designing, and targeting two or more Ca2+ proteins simultaneously may be explored; however, further clinical studies are essential to validate Ca2+ blockers’ anti-cancer efficacy.

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“…[9,10] So far, a variety of ion interference methods, including Ca 2+ , Cl − , Fe 2+ /Fe 3+ and Mn 2+ , have been successfully applied for anti-tumor therapy through combining interference of channel inhibitors and ion donors. [11][12][13][14] Zinc ions (Zn 2+ ) is a key auxiliary component in key metabolic regions of several enzyme molecules involved in protein synthesis, such as ribose nucleic acid (RNA) polymerase. [15] Excess Zn 2+ could block over-active calcium signal, thus selectively inhibiting the growth of cancer cells without affecting normal cells.…”

Section: Introductionmentioning

confidence: 99%

“Block and attack” strategy for tumor therapy through ZnO₂/siRNA/NIR‐mediating Zn²⁺‐overload and amplified oxidative stress

et al. 2023

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Intracellular zinc ion (Zn2+) accumulation disrupts the Zn2+ homeostasis, providing an ion‐overloading anticancer strategy with great potential. The self‐adaptation of tumor cells to ion concentration, however, puts forward higher requirements for the design of ion‐overloading strategy. Herein, “block and attack” antitumor strategy was applied through a composite nanomaterials (UHSsPZH NPs). The strategy demonstrated powerful ion interference ability through both “blocking” the efflux of excess Zn2+ via gene silencing and “attacking” tumor cells via target delivery of ZnO2. After cellular internalization, ZnO2 was degraded to Zn2+ and hydrogen peroxide (H2O2), and the gene expression of zinc transporter 1 (ZnT1) was silenced by targeting of released siRNA, which together caused intracellular Zn2+‐overload. Disorder of Zn2+ further interfered with intracellular Ca2+ homeostasis, inhibited the electron transport chain and promoted the production of endogenous reactive oxygen species (ROS), which assisted the “attack” to tumor cells together with the exogenous ROS generated by UHSsPZH NPs under 980 nm laser irradiation. In summary, this work supplies a “block and attack” strategy for the application of ion homeostasis interference in tumor therapy.

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Calcium-chelated nanosystem reversing cancer chemoresistance via replenishing intracellular calcium ions

Cited by 9 publications

References 36 publications

Multifaceted Roles of Copper Ions in Anticancer Nanomedicine

Multifaceted Roles of Copper Ions in Anticancer Nanomedicine

Dysregulation of calcium homeostasis in cancer and its role in chemoresistance

“Block and attack” strategy for tumor therapy through ZnO₂/siRNA/NIR‐mediating Zn²⁺‐overload and amplified oxidative stress

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Calcium-chelated nanosystem reversing cancer chemoresistance via replenishing intracellular calcium ions

Cited by 9 publications

References 36 publications

Multifaceted Roles of Copper Ions in Anticancer Nanomedicine

Multifaceted Roles of Copper Ions in Anticancer Nanomedicine

Dysregulation of calcium homeostasis in cancer and its role in chemoresistance

“Block and attack” strategy for tumor therapy through ZnO2/siRNA/NIR‐mediating Zn2+‐overload and amplified oxidative stress

Contact Info

Product

Resources

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“Block and attack” strategy for tumor therapy through ZnO₂/siRNA/NIR‐mediating Zn²⁺‐overload and amplified oxidative stress