Eradication Of Breast Cancer Cells Research Articles

Indocyanine Green‐Glycogen Conjugates for Near‐Infrared‐Triggered Photothermal Cancer Therapy

AbstractPhotothermal reagents sensitive to near‐infrared (NIR) light are promising imaging agents and therapeutics for anticancer applications because of the deep tissue penetration of NIR light, allowing for spatiotemporal control over the therapeutic activity, with minimal damage to normal tissues. Herein, a new class of NIR‐sensitive biopolymer‐based nanoparticles is presented by covalently conjugating indocyanine green (ICG) onto the surface of naturally occurring glycogen nanoparticles. The resulting ICG‐glycogen conjugates exhibit a markedly enhanced aqueous stability in comparison to free ICG molecules. Furthermore, an efficient light‐to‐heat conversion is enabled by ICG‐glycogen conjugates, as evidenced by the elevated temperatures of their aqueous solutions upon exposure to NIR light. Critically, ICG‐glycogen conjugates are capable of cell internalization, and under NIR irradiation the effective eradication of breast cancer cells, demonstrating their potential in photothermal therapy for cancer.

Anti-nucleolin Aptamer as a Boom in Rehabilitation of Breast Cancer.

Breast cancer is the second leading cause of cancer-related deaths. It is important to target the complex pathways using a suitable targeted delivery system. Targeted delivery systems can effectively act on cancer cells and lead to the annihilation of tumor proliferation. They mainly employ targeting agents like aptamers linked to the formulation. Based on the expression of the receptors on the surface of the cancer cells, suitable aptamers can be developed. AS1411 is one such aptamer that has the ability to bind to the over-expressed nucleolin present in breast cancer cells. Nucleolin is a phosphoprotein that is involved in various aspects, like cell growth, differentiation and survival. Mostly they are found in the nucleolus, nucleus, cytoplasm and cell surface. The shuttling effect of the nucleolin between the nucleus and cytoplasm serves as a bonus for the AS1411 aptamer. Because of the shutting effect, the internalization of the drug compound or chemotherapeutic drug inside the cell can be achieved. In this article, we have discussed nucleolin, anti-nucleolin aptamer, namely, AS1411, and its application in exhibiting various anticancer activities, including apoptosis, anti-angiogenesis, anti-metastasis, stimulation of tumor suppressor (i.e., P53), and inhibition of tumor inducer. Further, the ways of internalization, namely macropinocytosis, are also discussed. Additionally, we have also discussed the superiority of the aptamer compared to the antibodies as well as the limitations of the aptamers. By considering all the above parameters, we hope this aptamer will be effective in the management and eradication of breast cancer cells.

Augment the efficacy of eradicating metastatic lesions and tumor proliferation in breast cancer by honokiol-loaded pH-sensitive targeted lipid nanoparticles

Functionally-enabled delivery systems for aggressive lung metastases from breast cancer have been broadly examined, and the simultaneous inhibition of metastasis while fighting tumors persists as a provocative concern. We propose a valid strategy for delivering natural drugs-Honokiol (Hol) to achieve eradication of breast cancer cells and inhibition of pulmonary metastasis. A non-toxic degradable pH-sensitive polymer-PBAE for encapsulated Hol, and the outer layer was wrapped with Folate-DSPE-PEG2000 (FA/PBAE/Hol-NPs), which have strengthened stability, prolonged in vivo circulation time and efficiently targets tumor sites. FA/PBAE/Hol-NPs displayed dampening the capability of migration and invasion, elevated 4T1 uptake and boosted apoptosis. What’s more, 4T1 breast cancer model mice exhibited marked anti-tumor (Inhibition rate of 62.8 %) and lung metastasis suppression (Inhibition rate of 84.3 %). In parallel, histological immunofluorescence and immunohistochemical assays demonstrate higher apoptosis levels and repression of matrix metalloproteinase expression in mice, all of which are instrumental in inhibiting lung metastasis. Taken together, FA/PBAE/Hol-NPs can as an efficacious intravenous drug delivery system for the curative treatment of metastatic breast cancer.

Theoretical and photodynamic therapy characteristics of heteroatom doped detonation nanodiamonds linked to asymmetrical phthalocyanine for eradication of breast cancer cells

An amide mono substituted benzothiozole phthalocyanine: zinc(II) 3-(4-((3,17,23-tris(4-(benzo [d]thiazol-2-yl)phenoxy)-9-yl)oxy) phenyl)amide phthalocyanine (NH2BzPc) was covalently linked to undoped and heteroatom doped detonation nanodiamonds (DNDs): B@DNDs, P@DNDs, S@DNDs, N@DNDs, and S&N@DNDs There is a drastic decrease in highest occupied molecular orbital (HOMO) – lowest unoccupied molecular orbital (LUMO) energy gaps for nanoconjugates compared to DNDs alone. B@DNDs-NH2BzPc, S&N@DNDs-NH2BzPc, and P@DNDs-NH2BzPc showed superior photodynamic therapy (PDT) effects. DNDs-NH2BzPc also had a small HOMO-LUMO gap, but did not show improved PDT activity compared to the Pc alone, suggesting doping of DNDs is important. This study shows improved PDT effect on Michigan Cancer Foundation-7 breast cancer lines at 7.63%, 7.62% and 6.5% cell viability for P@DNDs-NH2BzPc, S&N@DNDs-NH2BzPc and B@DNDs-NH2BzPc, respectively.

Gold-coated iron oxide nanoparticles as a potential photothermal therapy agent to enhance eradication of breast cancer cells

Iron oxide nanoparticles (Fe3O4 NPs) possess unique physicochemical properties which make them great for biomedical applications. This study reports the development of gold (Au) coated Fe3O4 (Au-Fe3O4 NPs) for photothermal therapy to eradicate breast cancer cells (MCF-7). The spherical shape of monodisperse Au-Fe3O4 NPs with an average size of 20.8 nm was confirmed by TEM. The cell viability evaluation of Au-Fe3O4 NPs showed negligible toxicity toward MCF-7 cells after 24 h. Significant cell reduction was observed for MCF-7 (73.9%) cells following photothermal therapy at highest concentration of NPs (50 μgFe/ml) for 10 minutes illumination when compared with other intervention groups. It can be concluded that, the synthesized Au-Fe3O4 NPs is an effective and promising photothermal therapy agent for breast cancer treatment.

Toll-like receptor 4 and breast cancer: an updated systematic review.

Toll-like receptors (TLRs) may play dual roles in human cancers. TLR4 is a key molecule which may participate in both friend and foe roles against breast cancer. This review article collected recent data regarding the mechanisms used by TLR4 in the eradication of breast cancer cells and induction of the tumor cells, and discussed the mechanisms involved in the various functions of TLR4. The literature searches revealed that TLR4 is a key molecule that participates in breast cancer cell eradication or induction of breast cancer development and also transformation of the normal cells. TLR4 eradicates breast cancer cells via recognition of their DAMPs and then induces immune responses. Over-expression of TLR4 and also alterations in its signaling, including association of some intrinsic pathways such as TGF-β signaling and TP53, are the crucial factors to alter TLR4 functions against breast cancer.

Sensitization of HER2 Positive Breast Cancer Cells to Lapatinib Using Plants-Derived Isothiocyanates

Nearly 25% of all breast cancer is characterized by overexpression of HER2 (human epidermal growth factor receptor 2) which leads to overactivation of prosurvival signal transduction pathways, especially through Akt-mTOR-S6K kinases, and results in enhanced proliferation, migration, induction of angiogenesis, and apoptosis inhibition. Anti-HER2 targeted therapies, such as specific monoclonal antibodies or small-molecule tyrosine kinase inhibitors, even in combination, still seem to be insufficient due to incidence of primary or acquired resistance and prevalence of serious side-effects of these drugs. We assumed that combination of compounds that target different levels of the above-mentioned signal transduction pathway might be more effective in eradication of breast cancer cells. In our in vitro research we used a commercially available drug, lapatinib, acting at the level of the receptor in combination with 1 of the plant-derived isothiocyanates: sulforaphane, erucin, or sulforaphene, as it has been shown previously that sulforaphane inhibits Akt-mTOR-S6K1 pathway in breast cancer cells. We used 2 HER2 overexpressing breast cancer cell lines, SKBR-3 and BT-474. Combinations of the drug and isothiocyanates considerably decreased their viability. This action was synergistic and was accompanied by a decrease in phosphorylation of HER2, Akt, and S6. Combined treatment induced apoptosis more efficiently than either agent alone; however the most effective was a combination of lapatinib with erucin. These findings might support the optimization of therapy based on lapatinib treatment.

The eradication of breast cancer cells and stem cells by 8-hydroxyquinoline-loaded hyaluronan modified mesoporous silica nanoparticle-supported lipid bilayers containing docetaxel

Breast cancer stem cells (BCSCs), which can fully recapitulate the tumor origin and are often resistant to chemotherapy and radiotherapy, are currently considered as a major obstacle for breast cancer treatment. To achieve the goal of both targeting BCSCs and bulk breast cancer cells, we developed 8-hydroxyquinoline-loaded hyaluronan modified mesoporous silica nanoparticles (MSN)-supported lipid bilayers (HA-MSS) and docetaxel-loaded MSS. The results showed that the size of all the nanoparticles was smaller than 200 nm. BCSCs were enriched from MCF-7 cells by a sphere formation method and identified with the CD44+/CD24− phenotype. Quantitative and qualitative analysis demonstrated that HA promotes the uptake of HA-MSS in CD44-overexpressing MCF-7 mammospheres, revealing the mechanism of receptor-mediated endocytosis. DTX or DTX-loaded MSS showed much enhanced cytotoxicity against MCF-7 cells compared with MCF-7 mammospheres, whereas 8-HQ or 8-HQ-loaded HA-MSS showed much enhanced cytotoxicity against MCF-7 mammospheres compared with MCF-7 cells. In the MCF-7 xenografts in mice, the combination therapy with DTX-loaded MSS plus 8-HQ-loaded HA-MSS produced the strongest antitumor efficacy, with little systemic toxicity (reflecting by loss of body weight) in mice. Thus, this combination therapy may provide a potential strategy to improve the therapy of breast cancer by eradication of breast cancer cells together with BCSCs.

Feasibility of Eradication of Breast Cancer Cells Remaining in Postlumpectomy Cavity and Draining Lymph Nodes following Intracavitary Injection of Radioactive Immunoliposomes

Most diagnosed early stage breast cancer cases are treated by lumpectomy and adjuvant radiation therapy, which significantly decreases the locoregional recurrence but causes inevitable toxicity to normal tissue. By using a technique of preparing liposomes carrying technetium-99m ((99m)Tc), rhenium-186 ((186)Re), or rhenium-188 ((188)Re) radionuclides, as well as chemotherapeutic agents, or their combination, for cancer therapy with real time image-monitoring of pharmacokinetics and prediction of therapy effect, this study investigated the potential of a novel targeted focal radiotherapy with low systemic toxicity using radioactive immunoliposomes to treat both the surgical cavity and draining lymph nodes in a rat breast cancer xenograft positive surgical margin model. Immunoliposomes modified with either panitumumab (anti-EGFR) or bevacizumab (anti-VEGF) were remote loaded with (99m)Tc diagnostic radionuclide, and injected into the surgical cavity of female nude rats with positive margins postlumpectomy. Locoregional retention and systemic distribution of (99m)Tc-immunoliposomes were investigated by nuclear imaging, stereofluorescent microscopic imaging, and gamma counting. Histopathological examination of excised draining lymph nodes was performed. The locoregional retention of (99m)Tc-immunoliposomes in each animal was influenced by the physiological characteristics of the surgical site of individual animals. Panitumumab- and bevacizumab-liposome groups had higher intracavitary retention compared with the control liposome groups. Draining lymph node uptake was influenced by both the intracavitary radioactivity retention level and metastasis status. The panitumumab-liposome group had higher accumulation on the residual tumor surface and in the metastatic lymph nodes. Radioactive liposomes that were cleared from the cavity were metabolized quickly and accumulated at low levels in vital organs. Therapeutic radionuclide-carrying specifically targeted panitumumab- and bevacizumab-liposomes have increased potential compared to non-antibody targeted liposomes for postlumpectomy focal therapy to eradicate remaining breast cancer cells inside the cavity and draining lymph nodes with low systemic toxicity.

The eradication of breast cancer and cancer stem cells using octreotide modified paclitaxel active targeting micelles and salinomycin passive targeting micelles

Tumor stem cells have emerged as the new targets for anti-cancer therapy, besides tumor cells themselves. To eradicate both breast cancer cells and breast cancer stem cells which can not be eliminated by the conventional chemotherapy, octreotide (Oct)-modified paclitaxel (PTX)-loaded PEG- b-PCL polymeric micelles (Oct-M-PTX) and salinomycin (SAL)-loaded PEG- b-PCL polymeric micelles (M-SAL) were developed and investigated in combination. In this study, Oct that targets somatostatin receptors (SSTR) overexpressed in tumors including breast cancer, was coupled to the PEG end of PEG- b-PCL, and all the micelles were prepared using thin film hydration method. Results showed that the particle size of all the micelles was approximately 25–30 nm, and the encapsulation efficiency was >90%. Quantitative and qualitative analysis demonstrated that Oct facilitates the uptake of micelles in SSTR overexpressed breast cancer MCF-7 cells while free Oct inhibited cellular uptake of Oct-modified micelles, revealing the mechanism of receptor-mediated endocytosis. Breast cancer stem cells (side population cells, SP cells) were sorted from MCF-7 cells and identified with the CD44+/CD24− phenotype. M-SAL was capable of decreasing the proportion of SP cells, and its suppression was more potent in SP cells than that in cancer cells. As compared to PTX-loaded micelles (M-PTX), the inhibition of Oct-M-PTX against MCF-7 cells was stronger while such effect significantly increased when applying Oct-M-PTX in combination with M-SAL. In the MCF-7 xenografts, the combination therapy with Oct-M-PTX plus M-SAL produced the strongest antitumor efficacy, in accord with the combination treatment in vitro. Compared with free SAL, M-SAL was found to be more effective in suppressing breast cancer stem cells in vivo. Thus, this combination therapy may provide a strategy to improve treatment of breast cancers for eradication of breast cancer cells together with breast cancer stem cells.

Eradication of breast cancer cells in patients with distant metastasis: the finishing touches?

Cytotoxic agents are significantly active in breast cancer cells, but their usefulness has been limited in treating metastatic breast cancer (MBC). This has facilitated the development of an approach using molecular-targeted agents. Intrinsic subtypes including luminal A, luminal B, human epidermal growth factor receptor type 2 (HER2)-enriched, basal-like, and claudin-low tumors exhibit original drug responsiveness and clinical prognosis. Anti-HER2 treatments, trastuzumab or lapatinib, have demonstrated clinically significant efficacy. Poly ADP-ribose polymerase-1 inhibitors act against BRCA1-disabled breast cancer. Cancer stem cells could be the major obstacle to achieving a cure in systemic treatment. Extensive investigations are underway to develop novel agents that act on the genes or signaling of Hedgehog, Wnt, and Notch, which regulate cancer stem cells. Cancer cells undergo epithelial-mesenchymal transition (EMT) and acquire invasive properties. Breast cancer cells alter their phenotype in blood and bone marrow, e.g., circulating tumor cells or disseminated tumor cells. Cancer stem cells, like normal stem cells, may exist at niches in bone marrow. To achieve a cure for MBC, it is necessary to disrupt cancer stem cell-niche interactions or eradicate cancer stem cells. Traditional treatments with cytotoxic or endocrine agents require development in relation to intrinsic subtypes, stem cells, or EMT.