Leukocyte/platelet hybrid membrane-camouflaged dendritic large pore mesoporous silica nanoparticles co-loaded with photo/chemotherapeutic agents for triple negative breast cancer combination treatment

Cationic Mesoporous silica Nanoparticle coated with hyaluronic acid conjugated polymer (HA-Dual miRNA Np) facilitated enhanced dual miRNA loading, efficient delivery and significantly inhibited tumor growth as well as retarded metastasis in triple-negative breast cancer.

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CX-5461 Enhances the Efficacy of APR-246 via Induction of DNA Damage and Replication Stress in Triple-Negative Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22115782 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5782

Author(s):

Ashwini Makhale ◽

Devathri Nanayakkara ◽

Prahlad Raninga ◽

Kum Kum Khanna ◽

Murugan Kalimutho

Keyword(s):

Breast Cancer ◽

Dna Damage ◽

Triple Negative Breast Cancer ◽

Combination Treatment ◽

Triple Negative ◽

Annexin V ◽

Replication Stress ◽

Breast Cancer Cell Lines ◽

Combination Strategy

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking targeted therapy. Here, we evaluated the anti-cancer activity of APR-246, a P53 activator, and CX-5461, a RNA polymerase I inhibitor, in the treatment of TNBC cells. We tested the efficacy of individual and combination therapy of CX-5461 and APR-246 in vitro, using a panel of breast cancer cell lines. Using publicly available breast cancer datasets, we found that components of RNA Pol I are predominately upregulated in basal-like breast cancer, compared to other subtypes, and this upregulation is associated with poor overall and relapse-free survival. Notably, we found that the treatment of breast cancer cells lines with CX-5461 significantly hampered cell proliferation and synergistically enhanced the efficacy of APR-246. The combination treatment significantly induced apoptosis that is associated with cleaved PARP and Caspase 3 along with Annexin V positivity. Likewise, we also found that combination treatment significantly induced DNA damage and replication stress in these cells. Our data provide a novel combination strategy by utilizing APR-246 in combination CX-5461 in killing TNBC cells that can be further developed into more effective therapy in TNBC therapeutic armamentarium.

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Dual-Responsive Mesoporous Silica Nanoparticles Mediated Codelivery of Doxorubicin and Bcl-2 SiRNA for Targeted Treatment of Breast Cancer

The Journal of Physical Chemistry C ◽

10.1021/acs.jpcc.6b06759 ◽

2016 ◽

Vol 120 (39) ◽

pp. 22375-22387 ◽

Cited By ~ 51

Author(s):

Xiaojun Zhou ◽

Liang Chen ◽

Wei Nie ◽

Weizhong Wang ◽

Ming Qin ◽

...

Keyword(s):

Breast Cancer ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Targeted Treatment ◽

Dual Responsive

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Cationic Polymer Modified Mesoporous Silica Nanoparticles for Targeted siRNA Delivery to HER2+Breast Cancer

Advanced Functional Materials ◽

10.1002/adfm.201404629 ◽

2015 ◽

Vol 25 (18) ◽

pp. 2646-2659 ◽

Cited By ~ 98

Author(s):

Worapol Ngamcherdtrakul ◽

Jingga Morry ◽

Shenda Gu ◽

David J. Castro ◽

Shaun M. Goodyear ◽

...

Keyword(s):

Breast Cancer ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Sirna Delivery ◽

Cationic Polymer ◽

Her2 Breast Cancer

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Wee1 Inhibition Enhances the Anti-Tumor Effects of Capecitabine in Preclinical Models of Triple-Negative Breast Cancer.

10.21203/rs.2.22903/v1 ◽

2020 ◽

Author(s):

Todd Pitts ◽

Dennis M Simmons ◽

Stacey M Bagby ◽

Sarah J Hartman ◽

Betelehem W Yacob ◽

...

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Triple Negative Breast Cancer ◽

Combination Treatment ◽

Triple Negative ◽

Single Agent ◽

Cell Analysis ◽

Preclinical Models ◽

Pdx Models ◽

Live Cell Analysis

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive subtype defined by lack of hormone receptor expression and non-amplified HER2. Adavosertib (AZD1775) is a potent, small molecule, ATP-competitive inhibitor of the Wee1 kinase that potentiates the activity of many DNA-damaging chemotherapeutics and is currently in clinical development for multiple indications. The purpose of this study was to investigate the combination of AZD1775 and capecitabine/5-FU in preclinical TNBC models. Methods: TNBC cell lines were treated with AZD1775 and 5-FU and cellular proliferation was assessed in real-time using IncuCyte® Live Cell Analysis. Apoptosis was assessed via the Caspase-Glo 3/7 assay system. Western blotting was used to assess changes in expression of downstream effectors. TNBC PDX models were treated with AZD1775, capecitabine, or the combination and assessed for tumor growth inhibition. Results: From the initial PDX screen, two of the four TNBC PDX models demonstrated a better response in the combination treatment than either of the single agents. As confirmation, two PDX models were expanded for statistical comparison . Both PDX models demonstrated a significant growth inhibition in the combination versus either of the single agents. (TNBC012, p<0.05 combo vs adavosertib or capecitabine, TNBC013, p<0.01 combo vs adavosertib or capecitabine ). An enhanced antiproliferative effect was observed in the adavosertib/5-FU combination treatment as measured by live cell analysis. An increase in apoptosis was observed in two of the four cell lines in the combination when compared to single agent treatment. Treatment with single agent adavosertib resulted in an increase in p-CDC2 in a dose dependent manner that was also observed in the combination treatment. Similar results were observed with γH2AX in two of the four cell lines tested. No significant changes were observed in Bcl-xL following treatment in any of the cell lines. Conclusions: The combination of adavosertib and capecitabine/5-FU demonstrated enhanced combination effects both in vitro and in vivo in preclinical models of TNBC. These results support the clinical investigation of this combination in patients with TNBC, including those with brain metastasis given the CNS penetration of both agents.

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Large Pore Mesoporous Silica and Organosilica Nanoparticles for Pepstatin A Delivery in Breast Cancer Cells

Molecules ◽

10.3390/molecules24020332 ◽

2019 ◽

Vol 24 (2) ◽

pp. 332 ◽

Cited By ~ 9

Author(s):

Saher Rahmani ◽

Jelena Budimir ◽

Mylene Sejalon ◽

Morgane Daurat ◽

Dina Aggad ◽

...

Keyword(s):

Breast Cancer ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Cancer Cells ◽

Cathepsin D ◽

Breast Cancer Cells ◽

Potent Inhibitor ◽

Mesoporous Silica Nanoparticles ◽

Sol Gel ◽

Pepstatin A

(1) Background: Nanomedicine has recently emerged as a new area of research, particularly to fight cancer. In this field, we were interested in the vectorization of pepstatin A, a peptide which does not cross cell membranes, but which is a potent inhibitor of cathepsin D, an aspartic protease particularly overexpressed in breast cancer. (2) Methods: We studied two kinds of nanoparticles. For pepstatin A delivery, mesoporous silica nanoparticles with large pores (LPMSNs) and hollow organosilica nanoparticles (HOSNPs) obtained through the sol–gel procedure were used. The nanoparticles were loaded with pepstatin A, and then the nanoparticles were incubated with cancer cells. (3) Results: LPMSNs were monodisperse with 100 nm diameter. HOSNPs were more polydisperse with diameters below 100 nm. Good loading capacities were obtained for both types of nanoparticles. The nanoparticles were endocytosed in cancer cells, and HOSNPs led to the best results for cancer cell killing. (4) Conclusions: Mesoporous silica-based nanoparticles with large pores or cavities are promising for nanomedicine applications with peptides.

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