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.

Oxygen-producing proenzyme hydrogels for photodynamic mediated metastasis-inhibited combinational therapy

2021 ◽  
Author(s):  
Jiansheng Liu ◽  
Xueqin Qing ◽  
Qin Zhang ◽  
Ningyue Yu ◽  
Mengbin Ding ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Therapeutic Efficacy ◽  
Tumor Metastasis ◽  
Combinational Therapy ◽  
Hypoxic Tumor

Photodynamic therapy (PDT) has provided a promising approach for treatment of solid tumors, while the therapeutic efficacy is often limited due to hypoxic tumor microenvironment, resulting in tumor metastasis. We...

A fluorescence nanoprobe for detecting the effect of different oxygen and nutrient conditions on breast cancer cells migration and invasion

2021 ◽  
Author(s):  
Ping Zhou ◽  
Bo Liu ◽  
Mingming Luan ◽  
Na Li ◽  
Bo Tang
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Tumor Metastasis ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Fluorescence Nanoprobe

Cancer cell migration and invasion are initial steps for tumor metastasis that increases patient mortality. Tumor microenvironment is characterized by hypoxic and low nutrient-containing. Previous studies have suggested that hypoxia...

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 Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Erin A Bassett ◽  
Nicholas Tokarew ◽  
Ema A Allemano ◽  
Chantal Mazerolle ◽  
Katy Morin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Mouse Model ◽  
Tumor Cells ◽  
Tumor Stroma ◽  
Cerebellar Tumor ◽  
Short Term ◽  
Stromal Component ◽  
Tumor Types ◽  
The Relationship

The tumor microenvironment is a critical modulator of carcinogenesis; however, in many tumor types, the influence of the stroma during preneoplastic stages is unknown. Here we explored the relationship between pre-tumor cells and their surrounding stroma in malignant progression of the cerebellar tumor medulloblastoma (MB). We show that activation of the vascular regulatory signalling axis mediated by Norrin (an atypical Wnt)/Frizzled4 (Fzd4) inhibits MB initiation in the Ptch+/− mouse model. Loss of Norrin/Fzd4-mediated signalling in endothelial cells, either genetically or by short-term blockade, increases the frequency of pre-tumor lesions and creates a tumor-permissive microenvironment at the earliest, preneoplastic stages of MB. This pro-tumor stroma, characterized by angiogenic remodelling, is associated with an accelerated transition from preneoplasia to malignancy. These data expose a stromal component that regulates the earliest stages of tumorigenesis in the cerebellum, and a novel role for the Norrin/Fzd4 axis as an endogenous anti-tumor signal in the preneoplastic niche.

Organ tropism in solid tumor metastasis: an updated review

2021 ◽  
Author(s):  
Keywan Mortezaee
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Solid Tumor ◽  
Breast Cancer Cells ◽  
Tumor Metastasis ◽  
Cell Mass ◽  
Tumor Aggressiveness ◽  
Epigenetic Landscape ◽  
Growing Cell ◽  
Organ Tropism

Tumors are equipped with a highly complex machinery of interrelated events so as to adapt to hazardous conditions, preserve a growing cell mass and thrive at the site of metastasis. Tumor cells display metastatic propensity toward specific organs where the stromal milieu is appropriate for their further colonization. Effective colonization relies on the plasticity of tumor cells in adapting to the conditions of the new area by reshaping their epigenetic landscape. Breast cancer cells, for instance, are able to adopt brain-like or epithelial/osteoid features in order to pursue effective metastasis into brain and bone, respectively. The aim of this review is to discuss recent insights into organ tropism in tumor metastasis, outlining potential strategies to address this driver of tumor aggressiveness.

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.

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