The morphology of hydroxyapatite nanoparticles regulates clathrin-mediated endocytosis in melanoma cells and resultant anti-tumor efficiency

Wu, Hongfeng; Hua, Yuchen; Wu, Jinjie; Zeng, Qin; Yang, Xiao; Zhu, Xiangdong; Zhang, Xingdong

doi:10.1007/s12274-022-4220-y

Cited by 12 publications

(5 citation statements)

References 47 publications

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“…Compared to the rapid increase of tumor volume in the PBS group, CaCO 3 @L-PEG and M-CaCO 3 @L-PEG generated a moderate tumor inhibition effect, which could be attributed to the calcium overload and ROS production. 21,63,64 Moreover, the antitumor effect in the DM-CaCO 3 @L-PEG group was further enhanced owing to CuETs mediated paraptosis (Figure 6c). Furthermore, the tumor suppression efficacy of used NPs was investigated by H&E and Ki67 staining for observing histological changes among different groups.…”

Section: Resultsmentioning

confidence: 96%

Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca²⁺/Cu²⁺ Dual-Ions Nano Trap for Breast Cancer Treatment

Guo,

Gao,

et al. 2024

ACS Nano

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Regarded as one of the hallmarks of tumorigenesis and tumor progression, the evasion of apoptotic cell death would also account for treatment resistance or failure during cancer therapy. In this study, a Ca 2+ /Cu 2+ dual-ion "nano trap" to effectively avoid cell apoptosis evasion by synchronously inducing paraptosis together with apoptosis was successfully designed and fabricated for breast cancer treatment. In brief, disulfiram (DSF)-loaded amorphous calcium carbonate nanoparticles (NPs) were fabricated via a gas diffusion method. Further on, the Cu 2+ -tannic acid metal phenolic network was embedded onto the NPs surface by self-assembling, followed by mDSPE-PEG/lipid capping to form the DSF-loaded Ca 2+ /Cu 2+ dual-ions "nano trap". The as-prepared nanotrap would undergo acid-triggered biodegradation upon being endocytosed by tumor cells within the lysosome for Ca 2+ , Cu 2+ , and DSF releasing simultaneously. The released Ca 2+ could cause mitochondrial calcium overload and lead to hydrogen peroxide (H 2 O 2 ) overexpression. Meanwhile, Ca 2+ /reactive oxygen speciesassociated mitochondrial dysfunction would lead to paraptosis cell death. Most importantly, cell paraptosis could be further induced and strengthened by the toxic dithiocarbamate (DTC)−copper complexes formed by the Cu 2+ combined with the DTC, the metabolic products of DSF. Additionally, the released Cu 2+ will be reduced by intracellular glutathione to generate Cu + , which can catalyze the H 2 O 2 to produce a toxic hydroxyl radical by a Cu + -mediated Fenton-like reaction for inducing cell apoptosis. Both in vitro cellular assays and in vivo antitumor evaluations confirmed the cancer therapeutic efficiency by the dual ion nano trap. This study can broaden the cognition scope of dual-ion-mediated paraptosis together with apoptosis via a multifunctional nanoplatform.

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Section: Resultsmentioning

confidence: 96%

Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca²⁺/Cu²⁺ Dual-Ions Nano Trap for Breast Cancer Treatment

Guo,

Gao,

et al. 2024

ACS Nano

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“…Accumulated studies confirmed that HANPs themselves stimulated the production such as tumor necrosis factor α (TNFα) in macrophage, showing the typical features of immune adjuvant [21,22]. Additionally, HANPs have been explored as vaccine carriers due to their good antigen adsorption to improve the vaccine delivery for enhanced anti-tumor immunity [23]. Elevation of intracellular Ca 2+ in tumor cells was observed after HANPs treatment, which contributed to tumor cell apoptosis [24].…”

Section: Introductionmentioning

confidence: 95%

Hydroxyapatite nanoparticles drive the potency of Toll-like receptor 9 agonist for amplified innate and adaptive immune response

et al. 2022

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The potency of Toll-like receptor 9 (TLR9) agonist to drive innate immune response was limited due to immune suppression or tolerance during TLR9 signaling activation in immune cells. Herein we addressed this problem by introducing hydroxyapatite nanoparticles (HANPs) to CpG ODN (CpG), a TLR9 agonist. The study revealed that HANPs concentration and duration-dependently reprogramed the immune response by enhancing the secretion of immunostimulatory cytokines (tumor necrosis factor α (TNFα) or IL-6) while reducing the production of immunosuppressive cytokine (IL-10) in macrophages in response to CpG. Next, the enhanced immune response benefited from increased intracellular Ca 2+ in macrophage by the addition of HANPs. Further, we found exposure to HANPs impacted the mitochondrial function of macrophages in support of the synthesis of adenosine triphosphate (ATP), the production of nicotinamide adenine dinucleotide (NAD), and reactive oxygen species (ROS) in the presence or absence of CpG. In vaccinated mice model, only one vaccination with a mixture of CpG, HANPs, and OVA, a model antigen, allowed the development of a long-lasting balanced humoral immunity in mice without any histopathological change in the local injection site. Therefore, this study revealed that HANPs could modulate the intracellular calcium level, mitochondrial function, and immune response in immune cells, and suggested a potential combination adjuvant of HANPs and TLR9 agonist for vaccine development. Electronic Supplementary Material Supplementary material (TEM image, LDH activity, the Ca 2+ release in PBS, qRT-PCR analysis, H&E staining, and IL-6 level in the injection site and serum) is available in the online version of this article at 10.1007/s12274-022-4683-x.

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“…With the development of nanotechnology, nanoparticles (NPs) have opened new avenues for various biomedical applications such as drug/gene delivery, 1,2 molecular imaging 3,4 and diagnostic purposes. 5–7 The process of NP internalization into the cell is very important in most of the biomedical applications.…”

Section: Introductionmentioning

confidence: 99%

A computational study of the influence of nanoparticle shape on clathrin-mediated endocytosis

Li¹,

Zhang²,

Zhang³

et al. 2023

J. Mater. Chem. B

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The morphology of hydroxyapatite nanoparticles regulates clathrin-mediated endocytosis in melanoma cells and resultant anti-tumor efficiency

Cited by 12 publications

References 47 publications

Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca²⁺/Cu²⁺ Dual-Ions Nano Trap for Breast Cancer Treatment

Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca²⁺/Cu²⁺ Dual-Ions Nano Trap for Breast Cancer Treatment

Hydroxyapatite nanoparticles drive the potency of Toll-like receptor 9 agonist for amplified innate and adaptive immune response

A computational study of the influence of nanoparticle shape on clathrin-mediated endocytosis

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The morphology of hydroxyapatite nanoparticles regulates clathrin-mediated endocytosis in melanoma cells and resultant anti-tumor efficiency

Cited by 12 publications

References 47 publications

Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca2+/Cu2+ Dual-Ions Nano Trap for Breast Cancer Treatment

Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca2+/Cu2+ Dual-Ions Nano Trap for Breast Cancer Treatment

Hydroxyapatite nanoparticles drive the potency of Toll-like receptor 9 agonist for amplified innate and adaptive immune response

A computational study of the influence of nanoparticle shape on clathrin-mediated endocytosis

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Product

Resources

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Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca²⁺/Cu²⁺ Dual-Ions Nano Trap for Breast Cancer Treatment

Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca²⁺/Cu²⁺ Dual-Ions Nano Trap for Breast Cancer Treatment