Combinatorial photochemotherapy on liver cancer stem cells with organoplatinum(<scp>ii</scp>) metallacage-based nanoparticles

Yang, Beng; Liu, Hua; Huang, Yang; Chen, Wei; Wu, Jingban; Feng, Xiaode; Tong, Rongliang; Yu, Hanxi; Chen, Yunhao; Lv, Zhen; Sun, Weijian; He, Bin; Wu, Jian; Yu, Guocan; Mao, Zhengwei; Zheng, Shusen

doi:10.1039/c9tb01299k

Cited by 28 publications

(16 citation statements)

References 39 publications

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“…Another study utilized silver nanoparticles as a catalyst for ROS over-production to modify gene expression and protein alteration in mouse embryonic stem cells, affecting their self-renewal and proliferation capacity [ 72 ]. Moreover, organoplatinum (II) metallacage-loaded nanoparticles demonstrated their ability to inhibit liver CSC spheroid formation under near-infrared laser irradiation by generating ROS, resulting in the disruption of MMP, causing damage to the mitochondrial membrane, and triggering cell apoptosis [ 73 ]. According to the aforementioned findings, we strongly recommend the use of TiOxNPs as a synergistic drug with radiation therapy to eradicate pancreatic CSCs and inhibit EMT and metastasis through the over-production of ROS.…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species-inducing titanium peroxide nanoparticles as promising radiosensitizers for eliminating pancreatic cancer stem cells

Salah

Akasaka

Shimizu

et al. 2022

J Exp Clin Cancer Res

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Background Despite recent advances in radiotherapy, radioresistance in patients with pancreatic cancer remains a crucial dilemma for clinical treatment. Cancer stem cells (CSCs) represent a major factor in radioresistance. Developing a potent radiosensitizer may be a novel candidate for the eradication of pancreatic CSCs. Methods CSCs were isolated from MIA PaCa-2 and PANC1 human pancreatic cancer cell lines. Titanium peroxide nanoparticles (TiOxNPs) were synthesized from titanium dioxide nanoparticles (TiO2NPs) and utilized as radiosensitizers when added one hour prior to radiation exposure. The antitumor activity of this novel therapeutic strategy was evaluated against well-established pancreatic CSCs model both in vitro and in vivo. Results It is shown that TiOxNPs combined with ionizing radiation exhibit anti-cancer effects on radioresistant CSCs both in vitro and in vivo. TiOxNPs exhibited a synergistic effect with radiation on pancreatic CSC-enriched spheres by downregulating self-renewal regulatory factors and CSC surface markers. Moreover, combined treatment suppressed epithelial-mesenchymal transition, migration, and invasion properties in primary and aggressive pancreatic cancer cells by reducing the expression of proteins relevant to these processes. Notably, radiosensitizing TiOxNPs suppressed the growth of pancreatic xenografts following primary or dissociating sphere MIA PaCa-2 cell implantation. It is inferred that synergy is formed by generating intolerable levels of reactive oxygen species (ROS) and inactivating the AKT signaling pathway. Conclusions Our data suggested the use of TiOxNPs in combination with radiation may be considered an attractive therapeutic strategy to eliminate pancreatic CSCs.

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Section: Discussionmentioning

confidence: 99%

Reactive oxygen species-inducing titanium peroxide nanoparticles as promising radiosensitizers for eliminating pancreatic cancer stem cells

Salah

Akasaka

Shimizu

et al. 2022

J Exp Clin Cancer Res

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“…Protein concentration was measured by Bradford assay (Bio-Rad Laboratories, Inc., Hercules, USA). Western blots were performed as previously described [ 50 ].…”

Section: Methodsmentioning

confidence: 99%

High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN/Akt pathway in hepatocellular carcinoma

et al. 2020

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Exosomes play an important role in intercellular communication and metastatic progression of hepatocellular carcinoma (HCC). However, cellular communication between heterogeneous HCC cells with different metastatic potentials and the resultant cancer progression are not fully understood in HCC. Here, HCC cells with high-metastatic capacity (97hm and Huhm) were constructed by continually exerting selective pressure on primary HCC cells (MHCC-97H and Huh7). Through performing exosomal miRNA sequencing in HCC cells with different metastatic potentials (MHCC-97H and 97hm), many significantly different miRNA candidates were found. Among these miRNAs, miR-92a-3p was the most abundant miRNA in the exosomes of highly metastatic HCC cells. Exosomal miR92a-3p was also found enriched in the plasma of HCC patient-derived xenograft mice (PDX) model with high-metastatic potential. Exosomal miR-92a-3p promotes epithelial-mesenchymal transition (EMT) in recipient cancer cells via targeting PTEN and regulating its downstream Akt/Snail signaling. Furthermore, through mRNA sequencing in HCC cells with different metastatic potentials and predicting potential transcription factors of miR92a-3p, upregulated transcript factors E2F1 and c-Myc were found in high-metastatic HCC cells promote the expression of cellular and exosomal miR-92a-3p in HCC by directly binding the promoter of its host gene, miR17HG. Clinical data showed that a high plasma exosomal miR92a-3p level was correlated with shortened overall survival and disease-free survival, indicating poor prognosis in HCC patients. In conclusion, hepatoma-derived exosomal miR92a-3p plays a critical role in the EMT progression and promoting metastasis by inhibiting PTEN and activating Akt/Snail signaling. Exosomal miR92a-3p is a potential predictive biomarker for HCC metastasis, and this may provoke the development of novel therapeutic and preventing strategies against metastasis of HCC.

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“…The effect of ROS on the function of mitochondria has always been one of the research focuses of CSCs. ROS produced through PDT can induce apoptosis through increased mitochondrial membrane potential[ 111 ]. Studies have shown that mitochondrial photooxidative stress can cause a large number of lipid peroxidation reactions in the mitochondrial membrane, leading to rapid changes in the MMP, which stimulates pressure-dependent anion channels [voltage-dependent anion channels (VDACs)][ 112 ] and promotes the opening of the permeability transition pore complex[ 113 , 114 ], thereby releasing cytochrome C (Cyt C)[ 115 , 116 ] into the cytoplasm.…”

Section: Impact Of Ros From Pdt On Cscsmentioning

confidence: 99%

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

Zhang

Wang

et al. 2020

WJSC

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Photodynamic therapy (PDT) is an effective and promising cancer treatment. PDT directly generates reactive oxygen species (ROS) through photochemical reactions. This oxygen-dependent exogenous ROS has anti-cancer stem cell (CSC) effect. In addition, PDT may also increase ROS production by altering metabolism, endoplasmic reticulum stress, or potential of mitochondrial membrane. It is known that the half-life of ROS in PDT is short, with high reactivity and limited diffusion distance. Therefore, the main targeting position of PDT is often the subcellular localization of photosensitizers, which is helpful for us to explain how PDT affects CSC characteristics, including differentiation, self-renewal, apoptosis, autophagy, and immunogenicity. Broadly speaking, excess ROS will damage the redox system and cause oxidative damage to molecules such as DNA, change mitochondrial permeability, activate unfolded protein response, autophagy, and CSC resting state. Therefore, understanding the molecular mechanism by which ROS affect CSCs is beneficial to improve the efficiency of PDT and prevent tumor recurrence and metastasis. In this article, we review the effects of two types of photochemical reactions on PDT, the metabolic processes, and the biological effects of ROS in different subcellular locations on CSCs.

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Combinatorial photochemotherapy on liver cancer stem cells with organoplatinum(ii) metallacage-based nanoparticles

Abstract: Metallacage-based nanoparticles have superior therapeutic performance against liver cancer stem cells in both traditional 2D model and 3D multicellular spheroids, providing a promising strategy for efficient cancer treatment.

Cited by 28 publications

References 39 publications

Reactive oxygen species-inducing titanium peroxide nanoparticles as promising radiosensitizers for eliminating pancreatic cancer stem cells

Reactive oxygen species-inducing titanium peroxide nanoparticles as promising radiosensitizers for eliminating pancreatic cancer stem cells

High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN/Akt pathway in hepatocellular carcinoma

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

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