Cancer Therapy
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2021 ◽  
Vol 19 (1) ◽  
Yuqi Wang ◽  
Xiang Gong ◽  
Jie Li ◽  
Hong Wang ◽  
Xiaoxuan Xu ◽  

AbstractCancer cells and cancer stem cells (CSCs) are the major players of cancer malignancy and metastasis, but they are extremely difficult to access. Inspired by the vital role of macrophages and microvesicle-mediated cell–cell communication in tumors, we herein designed M2 macrophage microvesicle-inspired nanovehicle of cabazitaxel (M-CFN) to promote accessibility to cancer cells and CSCs in tumors. In the 4T1 tumor model, M-CFN flexibly permeated the tumor mass, accessed cancer cells and CD90-positive cells, and significantly promoted their entry into CSC fractions in tumors. Moreover, M-CFN treatment profoundly eliminated aldehyde dehydrogenase (ALDH)-expressing CSCs in 4T1 and MCF-7 tumors, produced notable depression of tumor growth and caused 93.86% suppression of lung metastasis in 4T1 models. Therefore, the M2 macrophage microvesicle-inspired nanovehicle provides an encouraging strategy to penetrate the tumor tissues and access these insult cells in tumors for effective cancer therapy. Graphical Abstract

2021 ◽  
Vol 19 (1) ◽  
Xiang Pan ◽  
Yuchen Qi ◽  
Zhen Du ◽  
Jian He ◽  
Sheng Yao ◽  

Abstract Background Colorectal cancer is a common malignancy occurring in the digestive system and ranks second in cancer mortality worldwide. In colorectal cancer, hydrogen sulfide (H2S) is selectively upregulated, resulting in the further exacerbation of the disease. Therefore, the clearance of H2S and the regulation of the enzymes on the H2S pathways are of great significance for colorectal cancer therapy. Methods Here, we investigated the H2S content in various clinical tumor tissues from patients and confirmed that overproduced concentration of H2S in colorectal cancer. Accordingly, we developed an H2S-responsive nanoplatform based on zinc oxide coated virus-like silica nanoparticles (VZnO) for the therapy of colorectal cancer. Results Owing to its excellent H2S scavenging ability, VZnO could effectively reduce H2S content in colorectal cancer to prohibit the growth of CT26 and HCT116 colorectal cancer cells. Moreover, the removal of H2S in colorectal cancer also leads to tumor inhibition through activating ferroptosis, a non-apoptotic form of cell death. The biosafety-related toxicological and pathological analysis confirmed the low toxicity and high safety of VZnO in colorectal cancer treatment. Furthermore, as an H2S-responsible nanosystem, VZnO appears to have no therapeutic effect on other non H2S rich cancers, such as the 4T1 breast cancer model. Conclusions We anticipate that the H2S-depletion-induced ferroptosis strategy using zinc oxide-based nanomaterials would provide insights in designing nanomedicines for colorectal cancer-target theranostics and may offer clinical promise. Graphic abstract

CCS Chemistry ◽  
2021 ◽  
pp. 1-29
Haiqiao Huang ◽  
Dandan Ma ◽  
Qiang Liu ◽  
Daipeng Huang ◽  
Xueze Zhao ◽  

Meng Zhang ◽  
Lijuan Gao ◽  
Yiping Ye ◽  
Xiaoyu Li

Small ◽  
2021 ◽  
pp. 2104567
Lu‐Lu Chen ◽  
Liang Zhao ◽  
Zhi‐Gang Wang ◽  
Shu‐Lin Liu ◽  
Dai‐Wen Pang

2021 ◽  
Aaron Becker von Rose ◽  
Kathrin Kobus ◽  
Bianca Bohmann ◽  
Matthias Trenner ◽  
Adam Wahida ◽  

2021 ◽  
Vol 18 ◽  
Razieh Mohammadian ◽  
Sussan Kabudanian Ardestani ◽  
Maliheh Safavi

Background: Cancer therapy is one of the most important challenges that human being faces. The abnormal activity of epidermal growth factor receptor tyrosine kinase (EGFR1) in tumors has been reported in many studies. Tyrosine kinase inhibitors are now commercially available for the treatment of a variety of cancers. Based on our previous studies, we assumed that a hybrid of aminopyrimidine derivatives as EGFR inhibitors and benzocheromen derivatives as cytotoxic agents can induce apoptosis in EGFR positive cancer cells. In the present study, the cytotoxic effect, ability of EGFR inhibition and apoptosis induction of some syndfrthetic benzochromene pyrimidine derivatives were investigated on MDA-MB231, SKBR3 and PC3 cell lines. Methods: The EGFR inhibition activity was determined using cell-based EGFR ELISA kit. Cell viability was determined by MTT assay in 2D and 3D cultures. The apoptosis was confirmed through different methods such as fluorescent staining, annexin V– propidium iodide double staining, DNA-Ladder assay, caspase-3 colorimetric assay, and nitric oxide assay. Results: The Results of the MTT assay showed that derivatives with different substituent exhibited differential cytotoxicity in three cancer cell lines, although in MDA-MB231 the cytotoxicity effect of compounds are more obvious than the other cell lines. Production of nitric oxide, caspase-3 activity and DNA-fragmentation was significant in MDA-MB231 and PC3 cells. SKBR3 cells, despite having the lowest apoptosis among these three cell lines, showed a significant EGFR inhibition in the ELISA assay. Conclusion: In this research we proved that hybrids of benzocheromen and amino pyrimidine could be effective on growth inhibition of cancer cell lines and may be used as a drug candidate for cancer therapy in the future.

2021 ◽  
Vol 11 (23) ◽  
pp. 11135
Jing Li ◽  
Lu-Xiang Zhao ◽  
Tao He ◽  
Wei-Wu Dong ◽  
Yue Yuan ◽  

Cold atmospheric plasmas (CAPs) used in plasma medicine have shown great potential in various aspects including wound healing, dermatology, cancer therapy, etc. It is one of the important issues to determine the plasma dosage in plasma medicine because it dominates the specific plasma treatment results. However, the multi-process interactions between CAPs and biological materials make it rather challenging to give an accurate and versatile definition for plasma dosage. In this study, the ratio of the discharge energy to the number of the treated in vitro kidney cells (mJ/cell) was employed as the unit of the plasma dosage. Additionally, inspired by basic knowledge of pharmacy, the median lethal dose (LD50) was employed to help estimate the plasma dosage. The experimental results show that the value of LD50 using the newly designed CAP Bio-Med Platform for the kidney cells is 34.67 mJ/cell. This biology-based method has the advantages of easy operation, independence of specific CAP sources, and also independence of complex interactions between CAPs and the treated biological targets, and consequently, may provide a new direction to quantitatively define the plasma dosage in various plasma medical applications.

2021 ◽  
Vol 12 (1) ◽  
Lidong Sun ◽  
Suli Lv ◽  
Tanjing Song

AbstractPrevalent dysregulation of epigenetic modifications plays a pivotal role in cancer. Targeting epigenetic abnormality is a new strategy for cancer therapy. Understanding how conventional oncogenic factors cause epigenetic abnormality is of great basic and translational value. O-GlcNAcylation is a protein modification which affects physiology and pathophysiology. In mammals, O-GlcNAcylation is catalyzed by one single enzyme OGT and removed by one single enzyme OGA. O-GlcNAcylation is affected by the availability of the donor, UDP-GlcNAc, generated by the serial enzymatic reactions in the hexoamine biogenesis pathway (HBP). O-GlcNAcylation regulates a wide spectrum of substrates including many proteins involved in epigenetic modification. Like epigenetic modifications, abnormality of O-GlcNAcylation is also common in cancer. Studies have revealed substantial impact on HBP enzymes and OGT/OGA by oncogenic signals. In this review, we will first summarize how oncogenic signals regulate HBP enzymes, OGT and OGA in cancer. We will then integrate this knowledge with the up to date understanding how O-GlcNAcylation regulates epigenetic machinery. With this, we propose a signal axis from oncogenic signals through O-GlcNAcylation dysregulation to epigenetic abnormality in cancer. Further elucidation of this axis will not only advance our understanding of cancer biology but also provide new revenues towards cancer therapy.

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