scholarly journals A GdW10@PDA-CAT Sensitizer with High-Z Effect and Self-Supplied Oxygen for Hypoxic-Tumor Radiotherapy

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 128
Author(s):  
Lixia Chen ◽  
Yang Zhang ◽  
Xinming Zhang ◽  
Ruijuan Lv ◽  
Rongtian Sheng ◽  
...  
Keyword(s):  
Dna Damage ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
X Ray ◽  
Cells In Culture ◽  
Ht29 Cells ◽  
Radiotherapy Field ◽  
Anticancer Treatment ◽  
Hypoxic Tumor

Anticancer treatment is largely affected by the hypoxic tumor microenvironment (TME), which causes the resistance of the tumor to radiotherapy. Combining radiosensitizer compounds and O2 self-enriched moieties is an emerging strategy in hypoxic-tumor treatments. Herein, we engineered GdW10@PDA-CAT (K3Na4H2GdW10O36·2H2O, GdW10, polydopamine, PDA, catalase, CAT) composites as a radiosensitizer for the TME-manipulated enhancement of radiotherapy. In the composites, Gd (Z = 64) and W (Z = 74), as the high Z elements, make X-ray gather in tumor cells, thereby enhancing DNA damage induced by radiation. CAT can convert H2O2 to O2 and H2O to enhance the X-ray effect under hypoxic TME. CAT and PDA modification enhances the biocompatibility of the composites. Our results showed that GdW10@PDA-CAT composites increased the efficiency of radiotherapy in HT29 cells in culture. This polyoxometalates and O2 self-supplement composites provide a promising radiosensitizer for the radiotherapy field.

A biomimetic nanozyme/camptothecin hybrid system for synergistically enhanced radiotherapy

2020 ◽  
Vol 8 (24) ◽  
pp. 5312-5319 ◽  
Author(s):  
Daoming Zhu ◽  
Meng Lyu ◽  
Wei Jiang ◽  
Meng Suo ◽  
Qinqin Huang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Hybrid System ◽  
Therapeutic Regimen ◽  
Hypoxic Tumor

Although radiotherapy (RT) has been an effective therapeutic regimen for regulating most solid tumors, its effect is limited by the hypoxic tumor microenvironment and radio-tolerance of tumor cells to a large extent.

scholarly journals Aneuploid Circulating Tumor-Derived Endothelial Cell (CTEC): A Novel Versatile Player in Tumor Neovascularization and Cancer Metastasis

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1539 ◽  
Author(s):  
Peter Ping Lin
Keyword(s):  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Vasculogenic Mimicry ◽  
Mesenchymal Transition ◽  
Tumor Neovascularization ◽  
Hypoxic Tumor

Hematogenous and lymphogenous cancer metastases are significantly impacted by tumor neovascularization, which predominantly consists of blood vessel-relevant angiogenesis, vasculogenesis, vasculogenic mimicry, and lymphatic vessel-related lymphangiogenesis. Among the endothelial cells that make up the lining of tumor vasculature, a majority of them are tumor-derived endothelial cells (TECs), exhibiting cytogenetic abnormalities of aneuploid chromosomes. Aneuploid TECs are generated from “cancerization of stromal endothelial cells” and “endothelialization of carcinoma cells” in the hypoxic tumor microenvironment. Both processes crucially engage the hypoxia-triggered epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndoMT). Compared to the cancerization process, endothelialization of cancer cells, which comprises the fusion of tumor cells with endothelial cells and transdifferentiation of cancer cells into TECs, is the dominant pathway. Tumor-derived endothelial cells, possessing the dual properties of cancerous malignancy and endothelial vascularization ability, are thus the endothelialized cancer cells. Circulating tumor-derived endothelial cells (CTECs) are TECs shed into the peripheral circulation. Aneuploid CD31+ CTECs, together with their counterpart CD31- circulating tumor cells (CTCs), constitute a unique pair of cellular circulating tumor biomarkers. This review discusses a proposed cascaded framework that focuses on the origins of TECs and CTECs in the hypoxic tumor microenvironment and their clinical implications for tumorigenesis, neovascularization, disease progression, and cancer metastasis. Aneuploid CTECs, harboring hybridized properties of malignancy, vascularization and motility, may serve as a unique target for developing a novel metastasis blockade cancer therapy.

scholarly journals Hypoxic Jumbo Spheroids On-A-Chip (HOnAChip): Insights into Treatment Efficacy

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4046
Author(s):  
Elena Refet-Mollof ◽  
Ouafa Najyb ◽  
Rodin Chermat ◽  
Audrey Glory ◽  
Julie Lafontaine ◽  
...  
Keyword(s):  
Dna Damage ◽  
Tumor Microenvironment ◽  
Cell Lines ◽  
Treatment Efficacy ◽  
Gold Standard ◽  
Soft Lithography ◽  
Sarcoma Cell ◽  
Hypoxic Tumor ◽  
Clinical Tools ◽  
User Friendly

Hypoxia is a key characteristic of the tumor microenvironment, too rarely considered during drug development due to the lack of a user-friendly method to culture naturally hypoxic 3D tumor models. In this study, we used soft lithography to engineer a microfluidic platform allowing the culture of up to 240 naturally hypoxic tumor spheroids within an 80 mm by 82.5 mm chip. These jumbo spheroids on a chip are the largest to date (>750 µm), and express gold-standard hypoxic protein CAIX at their core only, a feature absent from smaller spheroids of the same cell lines. Using histopathology, we investigated response to combined radiotherapy (RT) and hypoxic prodrug Tirapazamine (TPZ) on our jumbo spheroids produced using two sarcoma cell lines (STS117 and SK-LMS-1). Our results demonstrate that TPZ preferentially targets the hypoxic core (STS117: p = 0.0009; SK-LMS-1: p = 0.0038), but the spheroids’ hypoxic core harbored as much DNA damage 24 h after irradiation as normoxic spheroid cells. These results validate our microfluidic device and jumbo spheroids as potent fundamental and pre-clinical tools for the study of hypoxia and its effects on treatment response.

scholarly journals A Tumor Microenvironment-Responsive Poly(amidoamine) Dendrimer Nanoplatform for Hypoxia-Responsive Chemo/Chemodynamic Therapy

2021 ◽  
Author(s):  
Yingchao Hao ◽  
Yue Gao ◽  
Yu Fan ◽  
Changchang Zhang ◽  
Mengsi Zhan ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Breast Cancer Cells ◽  
Tumor Metastasis ◽  
Phenylboronic Acid ◽  
Pamam Dendrimers ◽  
Synergistic Inhibition ◽  
Catalytic Metal ◽  
Hypoxic Tumor ◽  
Tumor Types

Abstract Background: Chemodynamic therapy is a promising cancer treatment with specific therapeutic effect at tumor sites, since toxic hydroxyl radical (·OH) could only be generated by Fenton or Fenton-like reaction at the tumor microenvironment (TME) with low pH and high endogenous hydrogen peroxide (H2O2). However, the low concentration of catalytic metal ions, excessive glutathione (GSH) and aggressive hypoxia at tumor site seriously restrict its curative outcomes.Results: In this study, polyethylene glycol-phenylboronic acid (PEG-PBA)-modified generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers were synthesized as a targeted nanocarrier to chelate Cu(II) and then encapsulate hypoxia-sensitive drug tirapazamine (TPZ) by the formation of hydrophobic Cu(II)/TPZ complex for hypoxia-enhanced chemo/chemodynamic therapy. The formed G5.NHAc-PEG-PBA@Cu(II)/TPZ (GPPCT) with good stability could be specifically accumulated at tumors, efficiently taken up by tumor cells overexpressing sialic acid residues, and release Cu(II) ions and TPZ quickly in weakly acidic tumor sites via pH-sensitive dissociation of Cu(II)/TPZ. In vitro and in vivo experiments using murine breast cancer cells (4T1) demonstrated that the GPPCT nanoplatform could efficiently generate toxic ·OH in tumor cells while simultaneously deplete GSH, effectively kill hypoxic tumor cells by activated TPZ radicals, reduce tumor metastasis, and show no significant systemic toxicity.Conclusions: The targeted GPPCT nanoplatform may be developed for the synergistic inhibition of different tumor types by hypoxia-enhanced chemo/chemodynamic therapy.

scholarly journals Tumor Dormancy and Interplay with Hypoxic Tumor Microenvironment

2019 ◽  
Vol 20 (17) ◽  
pp. 4305 ◽  
Author(s):  
Elena Butturini ◽  
Alessandra Carcereri de Prati ◽  
Diana Boriero ◽  
Sofia Mariotto
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Current Knowledge ◽  
Tumor Dormancy ◽  
Hypoxic Conditions ◽  
Cycle Arrest ◽  
Regulatory Machinery ◽  
Key Factor ◽  
Hypoxic Tumor

The tumor microenvironment is a key factor in disease progression, local resistance, immune-escaping, and metastasis. The rapid proliferation of tumor cells and the aberrant structure of the blood vessels within tumors result in a marked heterogeneity in the perfusion of the tumor tissue with regions of hypoxia. Although most of the tumor cells die in these hypoxic conditions, a part of them can adapt and survive for many days or months in a dormant state. Dormant tumor cells are characterized by cell cycle arrest in G0/G1 phase as well as a low metabolism, and are refractive to common chemotherapy, giving rise to metastasis. Despite these features, the cells retain their ability to proliferate when conditions improve. An understanding of the regulatory machinery of tumor dormancy is essential for identifying early cancer biomarkers and could provide a rationale for the development of novel agents to target dormant tumor cell populations. In this review, we examine the current knowledge of the mechanisms allowing tumor dormancy and discuss the crucial role of the hypoxic microenvironment in this process.

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