clay and Breast-Neoplasms

Cancer recurrence and metastasis are worldwide challenges but current bimodular strategies such as combined radiotherapy and chemotherapy (CTX), and photothermal therapy (PTT) and immunotherapy have succeeded only in some limited cases. Thus in the present study, a multifunctional nanomedicine has been rationally designed via elegantly integrating three FDA-approved therapeutics, that is, indocyanine green (for PTT), doxorubicin (for CTX), and CpG (for immunotherapy) into the structure of layered double hydroxide (LDH) nanoparticles, aiming to completely prevent the recurrence and metastasis of invasive breast cancer. This multifunctional hybrid nanomedicine has been demonstrated to eliminate the primary tumor and efficiently prevent tumor recurrence and lung metastasis through combined PTT/CTX and induction of specific and strong immune responses mediated by the hybrid nanomedicine in a 4T1 breast cancer mouse model. Furthermore, the promoted in situ immunity has significantly inhibited the growth of reinoculated distant tumors. Altogether, our multifunctional LDH-based nanomedicine has showed an excellent efficacy in invasive cancer treatment using much lower doses of three FDA-approved therapeutics, providing a preclinical/clinical alternative to cost-effectively treat invasive breast cancer.

Topics: Animals; Breast Neoplasms; Clay; Female; Humans; Lung Neoplasms; MCF-7 Cells; Mice; Mice, Inbred BALB C; Nanomedicine; Nanoparticles; Neoplasm Invasiveness; Neoplasm Metastasis; Xenograft Model Antitumor Assays

Breast cancer (BrCa) preferentially spreads to bone and colonises within the bone marrow to cause bone metastases. To improve the outcome of patients with BrCa bone metastasis, we need to understand better the mechanisms underlying bone metastasis. Researchers have relied heavily upon in vivo xenografts due to limited availability of human bone metastasis samples. A significant limitation of these is that they do not have a human bone microenvironment. To address this issue, we have developed a nanoclay-based 3D in vitro model of BrCa bone metastasis using human mesenchymal stem cells (MSCs) and human BrCa cells mimicking late stage of BrCa pathogenesis at the metastatic site. This 3D model can provide a microenvironment suitable for cell-cell and cell-matrix interactions whilst retaining the behaviour of BrCa cells with different metastasis potential (i.e., highly metastatic MDA-MB-231 and low metastatic MCF-7) as shown by the production of alkaline phosphatase and matrix metalloproteinase-9. The sequential culture of MSCs with MCF-7 exhibited 3D tumouroids formation and also occurrence of mesenchymal to epithelial transition of cancer metastasis as evidenced by gene expression and immunocytochemistry. The unique and distinct behaviour of highly metastatic MDA-MB-231 and the low metastatic MCF-7 was observed at the bone metastasis site. The changes to migratory capabilities and invasiveness in MDA-MB-231 in comparison with tumour growth with MCF-7 was observed. Together, a novel bone-mimetic 3D in vitro BrCa model has been developed that could be used to study mechanisms governing the later stage of cancer pathogenesis in bone.

Topics: Bone Neoplasms; Breast Neoplasms; Cell Culture Techniques; Clay; Female; Humans; MCF-7 Cells; Models, Biological; Nanostructures; Neoplasm Metastasis; Tissue Engineering

Halloysite nanotubes (HNTs) are natural aluminosilicates with unique hollow lumen structure, also having high specific area, good biocompatibility, nontoxicity, and low price. Here, we designed a chitosan oligosaccharide-grafted HNTs (HNTs-g-COS) as a doxorubicin (DOX) carrier for treating breast cancer both in vitro and in vivo. The structure of HNTs-g-COS was first characterized by various methods. HNTs-g-COS showed positively charged surface and improved hemocompatibility. DOX-loaded HNTs-g-COS (DOX@HNTs-g-COS) released in cell lysate in a controlled manner. The IC

Topics: Aluminum Silicates; Animals; Breast Neoplasms; Cell Line, Tumor; Chitosan; Clay; Doxorubicin; Humans; Mice; Nanotubes; Oligosaccharides

Circulating tumor cells (CTCs) can be used clinically to treat cancer. As a diagnostic tool, the CTC count can be used to follow disease progression, and as a treatment tool, CTCs can be used to rapidly develop personalized therapeutic strategies. To be effectively used, however, CTCs must be isolated at high purity without inflicting cellular damage.. We designed a microscale flow device with a functionalized surface of E-selectin and antibody molecules against epithelial markers. The device was additionally enhanced with a halloysite nanotube coating. We created model samples in which a known number of labeled cancer cells were suspended in healthy whole blood to determine device capture efficiency. We then isolated and cultured primary CTCs from buffy coat samples of patients diagnosed with metastatic cancer.. Approximately 50% of CTCs were captured from model samples. Samples from 12 metastatic cancer patients and 8 healthy participants were processed in nanotube-coated or smooth devices to isolate CTCs. We isolated 20-704 viable CTCs per 3.75-mL sample, achieving purities of 18%-80% CTCs. The nanotube-coated surface significantly improved capture purities (P = 0.0004). Experiments suggested that this increase in purity was due to suppression of leukocyte spreading.. The device successfully isolates viable CTCs from both blood and buffy coat samples. The approximately 50% capture rate with purities >50% with the nanotube coating demonstrates the functionality of this device in a clinical setting and opens the door for personalized cancer therapies.

Topics: Aluminum Silicates; Antibodies; Antigens, Neoplasm; Antigens, Surface; Blood Buffy Coat; Breast Neoplasms; Cell Adhesion; Cell Adhesion Molecules; Cell Count; Cell Separation; Clay; E-Selectin; Epithelial Cell Adhesion Molecule; Female; Glutamate Carboxypeptidase II; Humans; Leukocytes; Lung Neoplasms; Male; Nanotubes; Neoplasm Metastasis; Neoplastic Cells, Circulating; Ovarian Neoplasms; Polyurethanes; Prostatic Neoplasms

Halloysite is natural aluminosilicate clay with hollow tubular structure which allows loading with low soluble drugs using their saturated solutions in organic solvents. Resveratrol, a polyphenol known for having antioxidant and antineoplastic properties, is loaded inside these clay nanotubes lumens. Release time of 48 h is demonstrated. Spectroscopic and ζ-potential measurements are used to study the drug loading/release and for monitoring the nanotube layer-by-layer (LbL) coating with polyelectrolytes for further release control. Resveratrol-loaded clay nanotubes are added to breast cell cultures for toxicity tests. Halloysite functionalization with LbL polyelectrolyte multilayers remarkably decrease nanotube self-toxicity. MTT measurements performed with a neoplastic cell lines model system (MCF-7) as function of the resveratrol-loaded nanotubes concentration and incubation time indicate that drug-loaded halloysite strongly increase of cytotoxicity leading to cell apoptosis.

Topics: Aluminum Silicates; Antioxidants; Breast Neoplasms; Clay; Humans; Kinetics; MCF-7 Cells; Microscopy, Electron, Transmission; Nanotubes; Resveratrol; Stilbenes

Invasive malignant breast cancers are typically branchy and benign breast tumors are typically smooth. It is of interest to characterize tumor branchiness (roughness) to differentiate invasive malignant breast cancer from noninvasive ones. In this study, we examined the shear modulus (G) to elastic modulus (E) ratio, G/E, as a quantity to describe model tumor interfacial roughness using a piezoelectric cantilever capable of measuring both tissue elastic modulus and tissue shear modulus. The piezoelectric cantilever used had two lead zirconate titanate layers to facilitate all-electrical elastic (shear) modulus measurements using one single device. We constructed model tissues with tumors by embedding one-dimensional (1D) corrugated inclusions and three-dimensional (3D) spiky-ball inclusions made of modeling clay in gelatin. We showed that for smooth inclusions, G/E was 0.3 regardless of the shear direction. In contrast, for a 1D corrugated rough inclusion G/E was 0.3 only when the shear was parallel to corrugation and G/E increased with an increasing angle between the shear direction and the corrugation. When the shear was perpendicular to corrugation, G/E became >0.7. For 3D isotropic spiky-ball inclusions we showed that the G/E depended on the degree of the roughness. Using the ratio s/r of the spike length (s) to the overall inclusion radius (r) as a roughness parameter, we showed that for inclusions with s/r larger than or equal to 0.28, the G/E ratio over the inclusions was larger than 0.7 whereas for inclusions with s/r less than 0.28, the G/E decreased with decreasing s/r to around 0.3 at s/r=0. In addition, we showed that the depth limit of the G/E measurement is twice the width of the probe area of the piezoelectric cantilever.

Topics: Aluminum Silicates; Anisotropy; Biomechanical Phenomena; Breast Neoplasms; Clay; Elastic Modulus; Electricity; Lead; Models, Anatomic; Neoplasm Invasiveness; Phantoms, Imaging; Shear Strength; Titanium; Zirconium

Topics: Aluminum Silicates; Breast Neoplasms; Clay; Humans; Mastectomy, Segmental; Models, Anatomic