scholarly journals Novel CD44-targeting and pH/redox-dual-stimuli-responsive core–shell nanoparticles loading triptolide combats breast cancer growth and lung metastasis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinfeng Shi ◽  
Yali Ren ◽  
Jiaqi Ma ◽  
Xi Luo ◽  
Jiaxin Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hyaluronic Acid ◽  
Drug Release ◽  
Lung Metastasis ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Systemic Toxicity ◽  
Migration And Invasion ◽  
Stimuli Responsive ◽  
Cd44 Targeting

Abstract Background The toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited the clinical application. Thus, we fabricated a CD44-targeting and tumor microenvironment pH/redox-sensitive nanosystem composed of hyaluronic acid-vitamin E succinate and poly (β-amino esters) (PBAEss) polymers to enhance the TPL-mediated suppression of breast cancer proliferation and lung metastasis. Results The generated TPL nanoparticles (NPs) had high drug loading efficiency (94.93% ± 2.1%) and a desirable average size (191 nm). Mediated by the PBAEss core, TPL/NPs displayed a pH/redox-dual-stimuli-responsive drug release profile in vitro. Based on the hyaluronic acid coating, TPL/NPs exhibited selective tumor cellular uptake and high tumor tissue accumulation capacity by targeting CD44. Consequently, TPL/NPs induced higher suppression of cell proliferation, blockage of proapoptotic and cell cycle activities, and strong inhibition of cell migration and invasion than that induced by free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and blocking lung metastasis with decreased systemic toxicity in a 4T1 breast cancer mouse model at an equivalent or lower TPL dosage compared with that of free TPL. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis and suppressed expression of matrix metalloproteinases, which contributed to inhibiting tumor growth and pulmonary metastasis. Conclusion Collectively, our results demonstrate that TPL/NPs, which combine tumor active targeting and pH/redox-responsive drug release with proapoptotic and antimobility effects, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity. Graphic Abstract

scholarly journals Novel CD44-Targeting and pH/redox Dual-Stimuli Responsive Core-Shell Nanoparticles Loading Triptolide to Combat Breast Cancer Growth and Lung Metastasis

2021 ◽  
Author(s):  
Jinfeng Shi ◽  
Yali Ren ◽  
Jiaqi Ma ◽  
Xi Luo ◽  
Jiaxin Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Release ◽  
Lung Metastasis ◽  
Cancer Progression ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Systemic Toxicity ◽  
Migration And Invasion ◽  
Drug Release Profile ◽  
Cd44 Targeting

Abstract BackgroundThe toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited its clinical application. Therefore, we fabricated a CD44-targeting and tumor-microenvironment pH/redox sensitive nanosystem, composed by hyaluronic acid-Vitamin E succinate (HA-VE) and Poly (β-Amino Esters) (PBAEss) polymers, to enhance the suppression of breast cancer proliferation and lung metastasis of TPL. ResultsThe generated TPL/NPs had the high drug loading efficiency (94.93 ± 2.1%) and a desirable average size (191 nm). Mediated by PBAEss core, TPL/NPs displayed a pH/redox dual stimuli drug release profile in vitro. Based on HA coating, TPL/NPs exhibited selective tumor-cellular uptake and high tumor-tissue accumulation capacity via targeting CD44. As a consequence, TPL/NPs showed higher cell proliferation suppression, pro-apoptosis and cell cycle arrest activities, and stronger inhibitory effects on cell migration and invasion than free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and block lung metastasis in a 4T1 breast cancer mice model at equivalent or lower TPL dosage compared to free TPL, with the decreased systemic toxicity. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis, suppressed expression of matrix metalloproteinases, which all these contributed to inhibit tumor growth and pulmonary metastasis. ConclusionCollectively, our results demonstrate that TPL/NPs, which integrates tumor active-targeting and pH/redox responsive drug release, pro-apoptosis, and anti-mobility, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity.

Redox-sensitive hyaluronic acid–paclitaxel conjugate micelles with high physical drug loading for efficient tumor therapy

2015 ◽  
Vol 6 (46) ◽  
pp. 8047-8059 ◽  
Author(s):  
Tingjie Yin ◽  
Jing Wang ◽  
Lifang Yin ◽  
Linjia Shen ◽  
Jianping Zhou ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Drug Release ◽  
Cellular Uptake ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Drug Conjugates ◽  
Self Assembled ◽  
Polymer Drug Conjugates

Characterization of targeted redox-sensitive micelles self-assembled from polymer–drug conjugates exhibiting conspicuous drug loading capabilities, selective cellular uptake, rapid intracellular disassembly and drug release is presented.

Efficacy in Treating Lung Metastasis of Invasive Breast Cancer with Functional Vincristine Plus Dasatinib Liposomes

Pharmacology ◽  
2017 ◽  
Vol 101 (1-2) ◽  
pp. 43-53 ◽  
Author(s):  
Fan Zeng ◽  
Rui-Jun Ju ◽  
Lei Liu ◽  
Hong-Jun Xie ◽  
Li-Min Mu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Metastasis ◽  
Nude Mice ◽  
Invasive Breast Cancer ◽  
Metastatic Breast ◽  
Current Treatment ◽  
Migration And Invasion ◽  
Induce Cell Cycle Arrest ◽  
M Phase

Background: The metastasis of breast cancer is the leading cause of death, while lung metastasis is a major clinical phenomenon in patients with invasive breast cancer. The current treatment option comprising surgery, radiation, and standard chemotherapy cannot achieve a satisfactory effect on the treatment of lung metastasis of breast cancer. In this study, we report the potential of preventing lung metastasis of invasive breast cancer using the newly developed functional vincristine plus dasatinib liposomes. Methods: The investigations were performed on invasive breast cancer MDA-MB-231 cells in vitro and in lung metastatic model of invasive breast cancer MDA-MB-231 cells in nude mice. Results: The functional drug liposomes were able to induce cell cycle arrest at G2/M phase, induce apoptosis, inhibit adhesion, migration, and invasion of breast cancer cells in vitro, and prevent lung metastasis of breast cancer in nude mice. Conclusion: These findings indicate a potential clinical use of functional vincristine plus dasatinib liposomes for treating metastatic breast cancer.

scholarly journals ITGA2is a target of miR-206 promoting cancer stemness and lung metastasis through enhancedACLYandCCND1expression in triple negative breast cancer

2019 ◽  
Author(s):  
Valery Adorno-Cruz ◽  
Andrew D. Hoffmann ◽  
Xia Liu ◽  
Brian Wray ◽  
Ruth A. Keri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Lipid Metabolism ◽  
Lung Metastasis ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Fatty Acid Biosynthesis ◽  
Migration And Invasion ◽  
Cancer Stemness

AbstractAccumulating evidence demonstrates that cancer stemness is essential for both tumor development and progression, regulated by multi-layer factors at genetic, epigenetic and micro-environmental levels. However, how to target stemness-driven plasticity and eliminate metastasis remains one of the biggest challenges in the clinic. We aim to identify novel molecular mechanisms underlying stemness of triple negative breast cancer (TNBC) which frequently metastasizes to the visceral organs but lacks targeted therapies. Following our previous discovery of miR-206 as an epigenetic suppressor of tumorigenesis and metastasis, we now report that the integrin receptor CD49b-encodingITGA2is an oncogenic target of miR-206 in TNBC.ITGA2knockdown abolished cancer stemness (mammosphere formation, pluripotency marker expression, and FAK phosphorylation), inhibited cell cycling, compromised migration and invasion, and thereby decreasing lung metastasis of TNBC. RNA sequencing analyses of breast cancer cells revealed thatITGA2knockdown inhibits gene expression essential for both classical integrin-regulated pathways (cell cycle, wounding response, protein kinase, etc) and newly identified pathways such as lipid metabolism. Notably,ACLY-encoded ATP citrate lyase is one of the top targets in CD49b-regulated lipid metabolism andCCND1-encoded Cyclin D1 represents regulation of cell cycle and many other pathways. ACLY, known to catalyze the formation of cytosolic acetyl-CoA for fatty acid biosynthesis, is indispensable for cancer stemness. Overexpression ofCCND1rescues the phenotype ofITGA2knockdown-induced cell cycle arrest. High expression levels of theITGA2/ACLY/CCND1axis are correlated with an unfavorable relapse-free survival of patients with high grade breast cancer, in both basal-like and other subtypes. This study identifiesITGA2as a potential therapeutic target of TNBC stemness and metastasis.

Natural Hydrogels Applied in Photodynamic Therapy

2020 ◽  
Vol 27 (16) ◽  
pp. 2681-2703 ◽  
Author(s):  
Zhipan Feng ◽  
Shiying Lin ◽  
Andrew McDonagh ◽  
Chen Yu
Keyword(s):  
Photodynamic Therapy ◽  
Hyaluronic Acid ◽  
Drug Release ◽  
Three Dimensional ◽  
Controlled Drug Release ◽  
Natural Polymers ◽  
Current Review ◽  
Design Variables ◽  
Cd44 Targeting

Natural hydrogels are three-dimensional (3D) water-retaining materials with a skeleton consisting of natural polymers, their derivatives or mixtures. Natural hydrogels can provide sustained or controlled drug release and possess some unique properties of natural polymers, such as biodegradability, biocompatibility and some additional functions, such as CD44 targeting of hyaluronic acid. Natural hydrogels can be used with photosensitizers (PSs) in photodynamic therapy (PDT) to increase the range of applications. In the current review, the pertinent design variables are discussed along with a description of the categories of natural hydrogels available for PDT.

Gold embedded chitosan nanoparticles with cell membrane mimetic polymer coating for pH-sensitive controlled drug release and cellular fluorescence imaging

2020 ◽  
pp. 088532822095259
Author(s):  
Ke Ma ◽  
Yongbin Cheng ◽  
Xinran Wei ◽  
Daijun Chen ◽  
Xiaoli Zhao ◽  
...  
Keyword(s):  
Drug Release ◽  
Fluorescence Imaging ◽  
Colloidal Stability ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Chitosan Nanoparticles ◽  
Fluorescence Emission ◽  
Controlled Drug Release ◽  
Ph Sensitive ◽  
One Pot

In this work, gold embedded chitosan nanoparticles (Au@CS NPs) were fabricated by a one-pot method. The benzaldehyde-terminated poly[(2-methacryloyloxy) ethyl phosphorylcholine] (PMPC) was applied to modification of the gold doped chitosan nanoparticles. The obtained Au@CS-PMPC NPs had the diameter of 135 nm with a narrow distribution. The size of the Au@CS-PMPC NPs, as well as the size of the embedded gold NPs, might be well-controlled by adjusting the feeding ratio between chitosan and HAuCl4. Furthermore, the Au@CS-PMPC NPs showed increased colloidal stability, high drug loading content, pH-responsive drug release, excellent biocompatibility and bright fluorescence emission. The results demonstrated that Au@CS-PMPC NPs showed a great potential for tumor therapy via the combination advantages of pH-sensitive controlled drug release and cellular fluorescence imaging.

One-pot synthesis of hollow PDA@DOX nanoparticles for ultrasound imaging and chemo-thermal therapy in breast cancer

Nanoscale ◽  
2019 ◽  
Vol 11 (45) ◽  
pp. 21759-21766 ◽  
Author(s):  
Tao Zhang ◽  
Zhenqi Jiang ◽  
Ting Xve ◽  
Shan Sun ◽  
Juan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ultrasound Imaging ◽  
Loading Rate ◽  
Drug Loading ◽  
Thermal Therapy ◽  
Stimuli Responsive ◽  
One Pot ◽  
Imaging Capability ◽  
One Pot Synthesis ◽  
High Drug Loading

A one-pot synthesis of hollow nanoparticles (PDA@DOX) used for breast cancer treatment with an extremely high drug loading rate and dual stimuli-responsive drug delivery capacity. PDA@DOX demonstrated good photothermal performance and ultrasound imaging capability.

Dual stimuli responsive hollow nanogels with IPN structure for temperature controlling drug loading and pH triggering drug release

Soft Matter ◽  
2011 ◽  
Vol 7 (18) ◽  
pp. 7992 ◽  
Author(s):  
Zhimin Xing ◽  
Congling Wang ◽  
Jie Yan ◽  
Li Zhang ◽  
Lan Li ◽  
...  
Keyword(s):  
Drug Release ◽  
Drug Loading ◽  
Stimuli Responsive

scholarly journals New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Zhang ◽  
Xiaofeng Huang ◽  
Jin Liu ◽  
Guo Chen ◽  
Chengjun Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liver Metastasis ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Lung Metastasis ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Integrated Analysis ◽  
Qrt Pcr ◽  
Non Coding Rnas

Abstract Background Bone is the most common site of metastatic breast cancer, and it is a leading cause of breast cancer-related death. This study aimed to explore bone metastasis-related long non-coding RNAs (lncRNAs) in breast cancer. Methods Four mRNA datasets and two lncRNA datasets of bone metastasis, lung metastasis and liver metastasis of breast cancer were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, as well as the overlap of the two groups, were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein–protein interaction (PPI) network construction of DEmRNAs were conducted. The cis nearby-targeted DEmRNAs of DElncRNAs were obtained. Quantitative real-time polymerase chain reactions (qRT-PCR) was used to detect the expression levels of selected DEmRNAs and DElncRNAs. LOC641518-lymphoid enhancer-binding factor 1 (LEF1) pair was selected to verify its role in migration and invasion capability of breast cancer cells by wounding healing assay and transwell invasion assay. Results A total of 237 DEmRNAs were obtained in bone metastasis compared with both lung metastasis and liver metastasis. A total of three DElncRNAs in bone metastasis compared with both lung metastasis and liver metastasis were obtained. A total of seven DElncRNA-nearby-targeted DEmRNA pairs and 15 DElncRNA-nearby-targeted DEmRNA pairs in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, were detected, respectively. Four cis LncRNA-mRNA interaction pairs were identified, which are LOC641518-LEF1, FLJ35024-Very Low Density Lipoprotein Receptor (VLDLR), LOC285972-Retinoic Acid Receptor Responder 2 (RARRES2) and LOC254896-TNF receptor superfamily member 10c (TNFRSF10C). qRT-PCR using clinical samples from our hospital confirms the bioinformatics prediction. siRNA knocking down LOC641518 down-regulates LEF1 mRNA expression, and reduces the migration and invasion capability of breast cancer cells. Conclusions We concluded that four LncRNA-mRNA pairs, including LOC641518-LEF1, may play a central role in breast cancer bone metastasis.

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