A Tumor Microenvironment-Responsive Co/ZIF-8/ICG/Pt Nanoplatform for Chemodynamic and Enhanced Photodynamic Antitumor Therapy

2022 ◽  
Author(s):  
Fan Jiang ◽  
Yajie Zhao ◽  
Chunzheng Yang ◽  
Ziyong Cheng ◽  
Min Liu ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Antitumor Therapy

Hypoxia and overexpression of hydrogen peroxide (H2O2) in tumor microenvironment (TME) are conducive to cancer cells proliferation, which greatly hinder cancer treatment. Here, we design a novel TME-responsive therapeutic nanoplatform...

Role of the Immune Component of Tumor Microenvironment in the Efficiency of Cancer Treatment: Perspectives for the Personalized Therapy

2017 ◽  
Vol 23 (32) ◽  
pp. 4807-4826 ◽  
Author(s):  
Marina Stakheyeva ◽  
Vladimir Riabov ◽  
Irina Mitrofanova ◽  
Nikolai Litviakov ◽  
Evgeny Choynzonov ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Immune Cells ◽  
Critical Factor ◽  
Cancer Diagnostics ◽  
Patient Specific ◽  
Intratumor Heterogeneity ◽  
Therapeutic Approaches

Despite significant progress in cancer diagnostics and development of novel therapeutic regimens, successful treatment of advanced forms of cancer is still a challenge and may require personalized therapeutic approaches. In this review, we analyzed major mechanisms responsible for tumor cells chemoresistance and emphasized that intratumor heterogeneity is a critical factor that limits efficiency of cancer treatment. Intratumor heterogeneity is caused by genomic instability in cancer cells, resulting in the selection of resistant clones. Moreover, cancer cells in solid tumors are surrounded by cellular and molecular microenvironment that actively influences tumor cell behavior. Local tumor microenvironment (TME) consisting of immune cells with diverse phenotypes and functions strongly contributes to intratumor heterogeneity and modulates responses to treatment. Thus, targeting specific components of TME is a novel treatment strategy that can improve the outcome of conventional anti-cancer therapy. Here, we discuss modern immunotherapeutic approaches based on targeting tumorinfiltrating immune cells including neutrophils, dendritic cells, NK cells, T cells, B cells and macrophages. Among those, tumor-associated macrophages (TAM) that display a pronounced heterogeneity and phenotypic plasticity appear to be a major component in the TME of solid tumors, and emerge as perspective targets for cancer immunotherapy. TAM intratumor heterogeneity and the possible existence of patient-specific phenotype signature generate the basis for the development of individualized TAM-based therapeutic approaches.

scholarly journals The Role of Platelets in the Tumor-Microenvironment and the Drug Resistance of Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 240 ◽  
Author(s):  
Phung Huong ◽  
Lap Nguyen ◽  
Xuan-Bac Nguyen ◽  
Sang Lee ◽  
Duc-Hiep Bach
Keyword(s):  
Drug Resistance ◽  
Growth Factors ◽  
Tumor Microenvironment ◽  
Treatment Failure ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Chemotherapeutic Drugs ◽  
Activated Platelets

Besides the critical functions in hemostasis, thrombosis and the wounding process, platelets have been increasingly identified as active players in various processes in tumorigenesis, including angiogenesis and metastasis. Once activated, platelets can release bioactive contents such as lipids, microRNAs, and growth factors into the bloodstream, subsequently enhancing the platelet–cancer interaction and stimulating cancer metastasis and angiogenesis. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated to be associated with platelets. Therefore, understanding how platelets contribute to the tumor microenvironment may potentially identify strategies to suppress cancer angiogenesis, metastasis, and drug resistance. Herein, we present a review of recent investigations on the role of platelets in the tumor-microenvironment including angiogenesis, and metastasis, as well as targeting platelets for cancer treatment, especially in drug resistance.

scholarly journals Ligand-Targeted Delivery of Photosensitizers for Cancer Treatment

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5317
Author(s):  
Piotr Gierlich ◽  
Ana I. Mata ◽  
Claire Donohoe ◽  
Rui M. M. Brito ◽  
Mathias O. Senge ◽  
...  
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Active Targeting ◽  
Cell Internalization ◽  
Tumor Accumulation ◽  
Skin Photosensitivity

Photodynamic therapy (PDT) is a promising cancer treatment which involves a photosensitizer (PS), light at a specific wavelength for PS activation and oxygen, which combine to elicit cell death. While the illumination required to activate a PS imparts a certain amount of selectivity to PDT treatments, poor tumor accumulation and cell internalization are still inherent properties of most intravenously administered PSs. As a result, common consequences of PDT include skin photosensitivity. To overcome the mentioned issues, PSs may be tailored to specifically target overexpressed biomarkers of tumors. This active targeting can be achieved by direct conjugation of the PS to a ligand with enhanced affinity for a target overexpressed on cancer cells and/or other cells of the tumor microenvironment. Alternatively, PSs may be incorporated into ligand-targeted nanocarriers, which may also encompass multi-functionalities, including diagnosis and therapy. In this review, we highlight the major advances in active targeting of PSs, either by means of ligand-derived bioconjugates or by exploiting ligand-targeting nanocarriers.

scholarly journals Dynamism, Sensitivity, and Consequences of Mesenchymal and Stem-Like Phenotype of Cancer Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Petra Gener ◽  
Joaquin Seras-Franzoso ◽  
Patricia González Callejo ◽  
Fernanda Andrade ◽  
Diana Rafael ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cell Types ◽  
Mesenchymal Phenotype ◽  
Metastatic Growth ◽  
Anticancer Treatment

There are remarkable similarities in the description of cancer stem cells (CSCs) and cancer cells with mesenchymal phenotype. Both cell types are highly tumorigenic, resistant against common anticancer treatment, and thought to cause metastatic growth. Moreover, cancer cells are able to switch between CSC and non-CSC phenotypes and vice versa, to ensure the necessary balance within the tumor. Likewise, cancer cells can switch between epithelial and mesenchymal phenotypes via well-described transition (EMT/MET) that is thought to be crucial for tumor propagation. In this review, we discuss whether, and to which extend, the CSCs and mesenchymal cancer cells are overlapping phenomena in terms of mechanisms, origin, and implication for cancer treatment. As well, we describe the dynamism of both phenotypes and involvement of the tumor microenvironment in CSC reversion and in EMT.

Multifunctional nanoparticles for targeting the tumor microenvironment to improve synergistic drug combinations and cancer treatment effects

2020 ◽  
Vol 8 (45) ◽  
pp. 10416-10427 ◽  
Author(s):  
Mei-Lin Chen ◽  
Chih-Jen Lai ◽  
Yi-Nan Lin ◽  
Chien-Ming Huang ◽  
Yu-Hsin Lin
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Treatment Effects ◽  
Prostate Tumor ◽  
Significant Enhancement ◽  
Ligand Recognition ◽  
Multifunctional Nanoparticles ◽  
Selectin Ligand ◽  
Synergistic Drug Combinations

Nanoparticles can internalize into cancer cells through CD44 and P-selectin ligand recognition, leading to significant enhancement of anti-prostate tumor activity.

scholarly journals Progress and Clinical Application of Single-Cell Transcriptional Sequencing Technology in Cancer Research

2021 ◽  
Vol 10 ◽  
Author(s):  
Jian Liu ◽  
Tianmin Xu ◽  
Yuemei Jin ◽  
Bingyu Huang ◽  
Yan Zhang
Keyword(s):  
Cancer Research ◽  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Single Cell ◽  
Cancer Cells ◽  
Research Progress ◽  
Tumor Evolution ◽  
Human Beings ◽  
First Choice ◽  
Daunting Challenge

Cancer has been a daunting challenge for human beings because of its clonal heterogeneity and compositional complexity. Tumors are composed of cancer cells and a variety of non-cancer cells, which together with the extracellular matrix form the tumor microenvironment. These cancer-related cells and components and immune mechanisms can affect the development and progression of cancer and are associated with patient diagnosis, treatment and prognosis. As the first choice for the study of complex biological systems, single-cell transcriptional sequencing (scRNA-seq) has been widely used in cancer research. ScRNA-seq has made breakthrough discoveries in tumor heterogeneity, tumor evolution, metastasis and spread, development of chemoresistance, and the relationship between the tumor microenvironment and the immune system. These results will guide clinical cancer treatment and promote personalized and highly accurate cancer treatment. In this paper, we summarize the latest research progress of scRNA-seq and its guiding significance for clinical treatment.

scholarly journals Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect

Cell Cycle ◽  
2011 ◽  
Vol 10 (15) ◽  
pp. 2504-2520 ◽  
Author(s):  
Ubaldo E. Martinez-Outschoorn ◽  
Zhao Lin ◽  
Casey Trimmer ◽  
Neal Flomenberg ◽  
Chenguang Wang ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Warburg Effect ◽  
The Warburg Effect

Resveratrol as an Adjuvant for Normal Tissues Protection and Tumor Sensitization

2020 ◽  
Vol 20 (2) ◽  
pp. 130-145 ◽  
Author(s):  
Keywan Mortezaee ◽  
Masoud Najafi ◽  
Bagher Farhood ◽  
Amirhossein Ahmadi ◽  
Dheyauldeen Shabeeb ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Clinical Studies ◽  
Normal Tissue ◽  
Medical Science ◽  
Treatment Modalities ◽  
Radiation Toxicity ◽  
Normal Tissues ◽  
Normal Tissue Toxicity

Cancer is one of the most complicated diseases in present-day medical science. Yearly, several studies suggest various strategies for preventing carcinogenesis. Furthermore, experiments for the treatment of cancer with low side effects are ongoing. Chemotherapy, targeted therapy, radiotherapy and immunotherapy are the most common non-invasive strategies for cancer treatment. One of the most challenging issues encountered with these modalities is low effectiveness, as well as normal tissue toxicity for chemo-radiation therapy. The use of some agents as adjuvants has been suggested to improve tumor responses and also alleviate normal tissue toxicity. Resveratrol, a natural flavonoid, has attracted a lot of attention for the management of both tumor and normal tissue responses to various modalities of cancer therapy. As an antioxidant and anti-inflammatory agent, in vitro and in vivo studies show that it is able to mitigate chemo-radiation toxicity in normal tissues. However, clinical studies to confirm the usage of resveratrol as a chemo-radioprotector are lacking. In addition, it can sensitize various types of cancer cells to both chemotherapy drugs and radiation. In recent years, some clinical studies suggested that resveratrol may have an effect on inducing cancer cell killing. Yet, clinical translation of resveratrol has not yielded desirable results for the combination of resveratrol with radiotherapy, targeted therapy or immunotherapy. In this paper, we review the potential role of resveratrol for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities.

Matrix Metalloproteinases (MMPs) in Targeted Drug Delivery: Synthesis of a Potent and Highly Selective Inhibitor against Matrix Metalloproteinase- 7

2020 ◽  
Vol 20 (27) ◽  
pp. 2459-2471
Author(s):  
Ling-Li Wang ◽  
Bing Zhang ◽  
Ming-Hua Zheng ◽  
Yu-Zhong Xie ◽  
Chang-Jiang Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Matrix Metalloproteinases ◽  
Cancer Treatment ◽  
Targeted Drug Delivery ◽  
Selective Inhibitor ◽  
Migration And Invasion ◽  
Side Chains ◽  
Mesenchymal Transition ◽  
Targeted Drug

Background: Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that play a key role in both physiological and pathological tissue degradation. MMPs have reportedly shown great potentials in the degradation of the Extracellular Matrix (ECM), have shown great potentials in targeting bioactive and imaging agents in cancer treatment. MMPs could provoke Epithelial to Mesenchymal Transition (EMT) of cancer cells and manipulate their signaling, adhesion, migration and invasion to promote cancer cell aggressiveness. Therefore, targeting and particularly inhibiting MMPs within the tumor microenvironment is an effective strategy for cancer treatment. Based on this idea, different MMP inhibitors (MMPIs) have been developed to manipulate the tumor microenvironment towards conditions appropriate for the actions of antitumor agents. Studies are ongoing to improve the selectivity and specificity of MMPIs. Structural optimization has facilitated the discovery of selective inhibitors of the MMPs. However, so far no selective inhibitor for MMP-7 has been proposed. Aims: This study aims to comprehensively review the potentials and advances in applications of MMPs particularly MMP-7 in targeted cancer treatment approaches with the main focus on targeted drug delivery. Different targeting strategies for manipulating and inhibiting MMPs for the treatment of cancer are discussed. MMPs are upregulated at all stages of expression in cancers. Different MMP subtypes have shown significant targeting applicability at the genetic, protein, and activity levels in both physiological and pathophysiological conditions in a variety of cancers. The expression of MMPs significantly increases at advanced cancer stages, which can be used for controlled release in cancers in advance stages. Methods: Moreover, this study presents the synthesis and characteristics of a new and highly selective inhibitor against MMP-7 and discusses its applications in targeted drug delivery systems for therapeutics and diagnostics modalities. Results: Our findings showed that the structure of the inhibitor P3’ side chains play the crucial role in developing an optimized MMP-7 inhibitor with high selectivity and significant degradation activities against ECM. Conclusion: Optimized NDC can serve as a highly potent and selective inhibitor against MMP-7 following screening and optimization of the P3’ side chains, with a Ki of 38.6 nM and an inhibitory selectivity of 575 of MMP-7 over MMP-1.

The Role of Cytokines in Interactions of Mesenchymal Stem Cells and Breast Cancer Cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Hariharan Jayaraman ◽  
Nalinkanth V. Ghone ◽  
Ranjith Kumaran R ◽  
Himanshu Dashora
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cell Communication ◽  
Extra Cellular Matrix ◽  
Cytokine Signaling ◽  
Cellular Matrix

: Mesenchymal stem cells because of its high proliferation, differentiation, regenerative capacity, and ease of availability have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and acts against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra-cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that acts as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as it is the leading member of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.

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