Spindle-Like Polypyrrole Hollow Nanocapsules as Multifunctional Platforms for Highly Effective Chemo-Photothermal Combination Therapy of Cancer Cells in Vivo

2014 ◽  
Vol 20 (37) ◽  
pp. 11826-11834 ◽  
Author(s):  
Yang Wang ◽  
Yun Xiao ◽  
Ruikang Tang
Keyword(s):  
Combination Therapy ◽  
Cancer Cells ◽  
Highly Effective

scholarly journals Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

2021 ◽  
Vol 14 (3) ◽  
pp. 254
Author(s):  
Afnan H. El-Gowily ◽  
Samah A. Loutfy ◽  
Ehab M. M. Ali ◽  
Tarek M. Mohamed ◽  
Mohammed A. Mansour
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mtor Pathway ◽  
Tumor Growth Inhibition ◽  
Autophagic Flux ◽  
Ki 67 ◽  
Mcf 7

Cancer is a complex devastating disease with enormous treatment challenges, including chemo- and radiotherapeutic resistance. Combination therapy demonstrated a promising strategy to target hard-to-treat cancers and sensitize cancer cells to conventional anti-cancer drugs such as doxorubicin. This study aimed to establish molecular profiling and therapeutic efficacy assessment of chloroquine and/or tioconazole (TIC) combination with doxorubicin (DOX) as anew combination model in MCF-7 breast cancer. The drugs are tested against apoptotic/autophagic pathways and related redox status. Molecular docking revealed that chloroquine (CQ) and TIC could be potential PI3K and ATG4B pathway inhibitors. Combination therapy significantly inhibited cancer cell viability, PI3K/AkT/mTOR pathway, and tumor-supporting autophagic flux, however, induced apoptotic pathways and altered nuclear genotoxic feature. Our data revealed that the combination cocktail therapy markedly inhibited tumor proliferation marker (KI-67) and cell growth, along with the accumulation of autophagosomes and elevation of LC3-II and p62 levels indicated autophagic flux blockage and increased apoptosis. Additionally, CQ and/or TIC combination therapy with DOX exerts its activity on the redox balance of cancer cells mediated ROS-dependent apoptosis induction achieved by GPX3 suppression. Besides, Autophagy inhibition causes moderately upregulation in ATGs 5,7 redundant proteins strengthened combinations induced apoptosis, whereas inhibition of PI3K/AKT/mTOR pathway with Beclin-1 upregulation leading to cytodestructive autophagy with overcome drug resistance effectively in curing cancer. Notably, the tumor growth inhibition and various antioxidant effects were observed in vivo. These results suggest CQ and/or TIC combination with DOX could act as effective cocktail therapy targeting autophagy and PI3K/AKT/mTOR pathways in MCF-7 breast cancer cells and hence, sensitizes cancer cells to doxorubicin treatment and combat its toxicity.

scholarly journals Potent pro-apoptotic combination therapy is highly effective in a broad range of cancers

2021 ◽  
Author(s):  
Antonella Montinaro ◽  
Itziar Areso Zubiaur ◽  
Julia Saggau ◽  
Anna-Laura Kretz ◽  
Rute M. M. Ferreira ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Cancer Cells ◽  
Standard Of Care ◽  
Therapy Resistance ◽  
Treatment Modalities ◽  
Cancer Resistance ◽  
Therapeutic Approaches ◽  
Highly Effective ◽  
Drastic Increase ◽  
New Treatment

AbstractPrimary or acquired therapy resistance is a major obstacle to the effective treatment of cancer. Resistance to apoptosis has long been thought to contribute to therapy resistance. We show here that recombinant TRAIL and CDK9 inhibition cooperate in killing cells derived from a broad range of cancers, importantly without inducing detectable adverse events. Remarkably, the combination of TRAIL with CDK9 inhibition was also highly effective on cancers resistant to both, standard-of-care chemotherapy and various targeted therapeutic approaches. Dynamic BH3 profiling revealed that, mechanistically, combining TRAIL with CDK9 inhibition induced a drastic increase in the mitochondrial priming of cancer cells. Intriguingly, this increase occurred irrespective of whether the cancer cells were sensitive or resistant to chemo- or targeted therapy. We conclude that this pro-apoptotic combination therapy has the potential to serve as a highly effective new treatment option for a variety of different cancers. Notably, this includes cancers that are resistant to currently available treatment modalities.

Polycatechol nanosheet: a superior nanocarrier for highly effective chemo-photothermal synergistic therapy in vivo

Nanoscale ◽  
2016 ◽  
Vol 8 (9) ◽  
pp. 5260-5267 ◽  
Author(s):  
J. Bai ◽  
X. D. Jia ◽  
Z. F. Ma ◽  
X. E. Jiang ◽  
X. P. Sun
Keyword(s):  
Cancer Cells ◽  
Highly Effective

A superior nanocarrier is facilely prepared and loaded with photothermal agent and drug, which can efficiently kill cancer cells in vivo.

Synthesis, characterization and in vitro and in vivo photodynamic activities of a gallium(iii) tris(ethoxycarbonyl)corrole

2017 ◽  
Vol 46 (29) ◽  
pp. 9481-9490 ◽  
Author(s):  
Zhao Zhang ◽  
Hua-Hua Wang ◽  
Hua-Jun Yu ◽  
Yu-Zhen Xiong ◽  
Hai-Tao Zhang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Signaling Cascade ◽  
Highly Effective

A gallium(iii) tris(ethoxycarbonyl)corrole is a highly effective photosensitizer against A549 cancer cells via p38 MAPK signaling cascade pathways.

scholarly journals Targeting MUS81 promotes the anticancer effect of WEE1 inhibitor and immune checkpoint blocking combination therapy via activating cGAS/STING signaling in gastric cancer cells

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Chengguo Li ◽  
Qian Shen ◽  
Peng Zhang ◽  
Tao Wang ◽  
Weizhen Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Anticancer Effect ◽  
Gastric Cancer Cells ◽  
Therapeutic Value

Abstract Background Identification of genomic biomarkers to predict the anticancer effects of indicated drugs is considered a promising strategy for the development of precision medicine. DNA endonuclease MUS81 plays a pivotal role in various biological processes during malignant diseases, mainly in DNA damage repair and replication fork stability. Our previous study reported that MUS81 was highly expressed and linked to tumor metastasis in gastric cancer; however, its therapeutic value has not been fully elucidated. Methods Bioinformatics analysis was used to define MUS81-related differential genes, which were further validated in clinical tissue samples. Gain or loss of function MUS81 cell models were constructed to elucidate the effect and mechanism of MUS81 on WEE1 expression. Moreover, the antitumor effect of targeting MUS81 combined with WEE1 inhibitors was verified using in vivo and in vitro assays. Thereafter, the cGAS/STING pathway was evaluated, and the therapeutic value of MUS81 for immunotherapy of gastric cancer was determined. Results In this study, MUS81 negatively correlated with the expression of cell cycle checkpoint kinase WEE1. Furthermore, we identified that MUS81 regulated the ubiquitination of WEE1 via E-3 ligase β-TRCP in an enzymatic manner. In addition, MUS81 inhibition could sensitize the anticancer effect of the WEE1 inhibitor MK1775 in gastric cancer in vitro and in vivo. Interestingly, when MUS81 was targeted, it increased the accumulation of cytosolic DNA induced by MK1775 treatment and activated the DNA sensor STING-mediated innate immunity in the gastric cancer cells. Thus, the WEE1 inhibitor MK1775 specifically enhanced the anticancer effect of immune checkpoint blockade therapy in MUS81 deficient gastric cancer cells. Conclusions Our data provide rational evidence that targeting MUS81 could elevate the expression of WEE1 by regulating its ubiquitination and could activate the innate immune response, thereby enhancing the anticancer efficacy of WEE1 inhibitor and immune checkpoint blockade combination therapy in gastric cancer cells.

scholarly journals A DM1-doped porous gold nanoshell system for NIR accelerated redox-responsive release and triple modal imaging guided photothermal synergistic chemotherapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Pengcheng Xu ◽  
Ru Wang ◽  
Wenqian Yang ◽  
Yanyan Liu ◽  
Dongsheng He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Multimodal Imaging ◽  
Breast Cancer Cells ◽  
M2 Macrophage ◽  
Tumour Targeting ◽  
Porous Gold

Abstract Background Although many treatments for breast cancer are available, poor tumour targeting limits the effectiveness of most approaches. Consequently, it is difficult to achieve satisfactory results with monotherapies. The lack of accurate diagnostic and monitoring methods also limit the benefits of cancer treatment. The aim of this study was to design a nanocarrier comprising porous gold nanoshells (PGNSs) co-decorated with methoxy polyethylene glycol (mPEG) and trastuzumab (Herceptin®, HER), a therapeutic monoclonal antibody that binds specifically to human epidermal receptor-2 (HER2)-overexpressing breast cancer cells. Furthermore, a derivative of the microtubule-targeting drug maytansine (DM1) was incorporated in the PGNSs. Methods Prepared PGNSs were coated with mPEG, DM1 and HER via electrostatic interactions and Au–S bonds to yield DM1-mPEG/HER-PGNSs. SK-BR-3 (high HER2 expression) and MCF-7 (low HER2) breast cancer cells were treated with DM1-mPEG/HER-PGNSs, and cytotoxicity was evaluated in terms of cell viability and apoptosis. The selective uptake of the coated PGNSs by cancer cells and subsequent intracellular accumulation were studied in vitro and in vivo using inductively coupled plasma mass spectrometry and fluorescence imaging. The multimodal imaging feasibility and synergistic chemo-photothermal therapeutic efficacy of the DM1-mPEG/HER-PGNSs were investigated in breast cancer tumour-bearing mice. The molecular mechanisms associated with the anti-tumour therapeutic use of the nanoparticles were also elucidated. Result The prepared DM1-mPEG/HER-PGNSs had a size of 78.6 nm and displayed excellent colloidal stability, photothermal conversion ability and redox-sensitive drug release. These DM1-mPEG/HER-PGNSs were taken up selectively by cancer cells in vitro and accumulated at tumour sites in vivo. Moreover, the DM1-mPEG/HER-PGNSs enhanced the performance of multimodal computed tomography (CT), photoacoustic (PA) and photothermal (PT) imaging and enabled chemo-thermal combination therapy. The therapeutic mechanism involved the induction of tumour cell apoptosis via the activation of tubulin, caspase-3 and the heat shock protein 70 pathway. M2 macrophage suppression and anti-metastatic functions were also observed. Conclusion The prepared DM1-mPEG/HER-PGNSs enabled nanodart-like tumour targeting, visibility by CT, PA and PT imaging in vivo and powerful tumour inhibition mediated by chemo-thermal combination therapy in vivo. In summary, these unique gold nanocarriers appear to have good potential as theranostic nanoagents that can serve both as a probe for enhanced multimodal imaging and as a novel targeted anti-tumour drug delivery system to achieve precision nanomedicine for cancers.

An In Vitro and In Vivo Study of Combination Therapy with Photogem®-Mediated Photodynamic Therapy and Cisplatin on Mouse Cancer Cells (CT-26)

2011 ◽  
Vol 29 (3) ◽  
pp. 155-160 ◽  
Author(s):  
Ruifeng Ge ◽  
Jin-Chul Ahn ◽  
Jang-In Shin ◽  
Chan Woong Bahk ◽  
Peijie He ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Combination Therapy ◽  
Cancer Cells ◽  
In Vivo Study

scholarly journals A DM1-doped porous gold nanoshell system for NIR accelerated redox-responsive release and triple modal imaging guided photothermal synergistic chemotherapy

2020 ◽  
Author(s):  
Yan Shen ◽  
Yuan Ding ◽  
Jiasheng Tu ◽  
Pengcheng Xu ◽  
Wenqian Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Multimodal Imaging ◽  
Electrostatic Interactions ◽  
Cell Uptake ◽  
Gold Nanoshell ◽  
Porous Gold

Abstract BackgroundAlthough many treatments are available for breast cancer, poor tumor targeting limits the effectiveness of most approaches and a monotherapy will yield satisfactory results difficultly. Furthermore, the lack of accurate diagnostic and tumor monitoring methods also limit the benefits of treatment. This study aimed to design a nanocarrier based on porous gold nanoshell (PGNSs) co-decorated with methoxy polyethylene glycol (mPEG) and trastuzumab (Herceptin®, HER) which can specifically bind to human epidermal receptor-2 (Her-2) over-expressed breast cancer cells and was incorporated with a derivative of the microtubule-targeting drug maytansine (DM1). PGNSs were prepared and then covered by the mPEG, DM1 and HER via the electrostatic interactions and Au-S bonds. The cytotoxicity of DM1-mPEG/HER-PGNSs on SK-BR-3 and MCF-7 cancer cells was evaluated in terms of cell viability and apoptosis analysis. The selective cancer cell uptake and accumulation were studied via ICP-MS and fluorescence imaging in vitro and in vivo. The multimodal imaging and synergistic chemo-photothermal therapeutic efficacy was investigated in breast cancer tumor-bearing mice. Then the molecular mechanism of the nanoparticles in anti-tumor applications were also elucidated.ResultThe as-prepared DM1-mPEG/HER-PGNSs with a size of 78.6 nm displayed excellent colloidal stability, photothermal conversion ability, and redox-sensitive drug release. These DM1-mPEG/HER-PGNSs exhibited selectively uptake by cancer cells in vitro and accumulation to tumor sites in vivo. Moreover, the DM1-mPEG/HER-PGNSs showed enhanced multimodal computed tomography (CT), photoacoustic (PA) and photothermal (PT) imaging and chemo-thermal combination therapy. The therapeutic mechanism involved the induction of tumor cell apoptosis via the activation of tubulin, caspase-3 and the HSP70 pathway. Meanwhile, the suppression of M2 macrophages and anti-metastatic functions were observed.ConclusionThese DM1-mPEG/HER-PGNSs would display nanodart-like targeting CT/PA/PT imaging in vivo and powerful tumor inhibition mediated by chemo-thermal combination therapy suggest that these unique gold nanocarriers are potential theranostic nanoagents that can serve both as a probe for enhanced multimodal imaging and as a novel targeted antitumor drug delivery system to achieve precision nanomedicine for cancer.

Treatment of chemoresistant ovarian cancer with sigma2/SMAC and cisplatin.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16508-e16508
Author(s):  
Ivy Wilkinson-Ryan ◽  
Dirk Spitzer ◽  
Robert Mach ◽  
Suwanna Vangveravong ◽  
Peter S Goedegebuure ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Platinum Resistance ◽  
Apoptotic Pathway ◽  
Major Barrier ◽  
Skov3 Cells

e16508 Background: Platinum resistance continues to be a major barrier to the successful treatment of ovarian cancer. Overexpression of the X-linked inhibitor of apoptosis proteins (XIAP) contribute to platinum resistance in ovarian cancer through inhibition of caspases and up regulation of Akt activity. Second mitochondrial-derived activators of caspases (SMAC) is an endogenous protein that binds to and reverses XIAP-mediated inhibition of caspases. In order to exploit the SMAC-mediated pro-apoptotic pathway pharmacologically, SMAC mimetics have been developed and shown to induce apoptosis in cancer cells in vitro and in vivo. Untargeted cytotoxic cancer drugs bind to both malignant and normal tissue leading to significant toxicity. We have shown previously that solid tumors upregulate the sigma-2 receptor. We have also shown that sigma-2 ligands are internalized into cancer cells and are therefore an appealing vehicle for tumor targeted therapy. The goal of this study is to test if a conjugate drug of sigma-2 ligand and a SMAC mimetic (sigma-2/SMAC) in combination with chemotherapy is capable of overcoming chemoresistance in ovarian cancer. Methods: SKOV3 and OVCAR3 ovarian cancer cell lines were treated with sigma2/SMAC (1-16μM) and/or cisplatin (.5-10μg/mL). Viability assays were used to detect cell death. Luminescence-based caspase assays were used to compare the activity of caspase-3, -7, and -9 between treatment groups to document involvement of the XIAP survival pathway. Results: We found that sigma2-SMAC is synergistic when used in combination with cisplatin. Compared to untreated cells, SKOV3 cells treated with sigma/2SMAC (4uM), cisplatin .5ug/mL, or combination therapy showed 52.6%, 117.7%, and 34.8% viability respectively (p<.05). Cisplatin and sigma2/SMAC remained synergistic at increasing doses. Similar results were observed in OVCAR3 cells. Caspase-3 and -7 increased in combination therapy 1.2-fold over Sigma/2SMAC alone (4uM) and 7-fold over cisplatin alone (.5ug/mL) in SKOV3 cells (p<.05). Conclusions: This study suggests that the sigma2/SMAC conjugate provides a targeted means for overcoming chemoresistance in ovarian cancer through inhibition of XIAP and activation of caspases.

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