Positive electrostatic therapy of metastatic tumors: selective induction of apoptosis in cancer cells by pure charges.

BACKGROUND: We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. METHODS: We interacted normal and cancer cell lines and animal tumors with PECs by connecting a charged patch to cancer cells and animal tumors. many biochemical, molecular and radiological assays were carried out on PEC treated and control samples. RESULTS: Correlative interactions between electrostatic charges and cancer cells contain critical unknown factors that influence cancer diagnosis and treatment. Different types of cell analyses prove PEC-based apoptosis induction in malignant cell lines. Flowcytometry and viability assay depict selective destructive effects of PEC on malignant breast cancer cells. Additionally, strong patterns of pyknotic apoptosis, as well as downregulation of proliferative-associated proteins (Ki67, CD31, and HIF-1α), were observed in histopathological and immunohistochemical patterns of treated mouse malignant tumors, respectively. Quantitative real-time polymerase chain reaction results demonstrate up/down-regulated apoptotic/proliferative transcriptomes (P21, P27, P53/CD34, integrin α5, vascular endothelial growth factor, and vascular endothelial growth factor receptor) in treated animal tumors. Expression of propidium iodide in confocal microscopy images of treated malignant tissues was another indication of the destructive effects of PECs on such cells. Significant tumor size reduction and prognosis improvement were seen in over 95% of treated mouse models with no adverse effects on normal tissues. CONCLUSION: We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. The findings were statistically and observationally significant when compared to radio/chemotherapy-treated mouse models. As a result, this nonionizing radiation may be used as a practical complementary approach with no discernible side effects after passing future human model studies.

Carbon nanotube based dielectric spectroscopy of tumor secretion; electrochemical lipidomics for cancer diagnosis.

Cell free diagnosis of cancer is one of the crucial fields in new generation of medical technology. In this regard, cancer detection based on coastal fluids secreted from the tissues (named as secretome) has attracted a lot of attention. Lipids are important macromolecules could be found with much higher concentrations in secretome of cancer tissues vs. normal ones. On the other hand, lipids are the main dielectric components of the secretome with respect to proteins and ions. Here for the first time we introduced an electrochemical lipidomics based on electrical impedance spectroscopy (EIS) of the secretomes to detect the cancerous samples due to the lipidic content of their secretions. The EIS sensor was fabricated by multiwall carbon nanotube (MWCNT) arrays as conductive and super hydrophobic materials to have great interactive surface with the lipidic content of the solution. Results of the tests on the secretions of more than 100 human biopsied breast tissues showed the promising match between the charge transfer resistance (RCT) of samples' secretions and pathological states of the tissues with meaningful boundary (up to 8 kΩ for normal and more than 13 kΩ for cancer samples). Mass spectroscopic analyses confirmed the higher content of lipids in cancer secretomes. Electrical lipidomics of the secretome shed new lights in cell free cancer diagnosis and could be applied as a complementary clinical approach in all of biopsy based diagnoses in future.

Microneedle-Based Generation of Microbubbles in Cancer Tumors to Improve Ultrasound-Assisted Drug Delivery.

Production of local microbubbles (MBs) with dense distribution in tumor environment is achieved by developing an integrated electrochemical stimulator on a microfabricated silicon needle covered by zinc-oxide nanowires (ZnONWs). MBs are then exploded by external ultrasonic actuation, which induce microcavitations in tumor cells followed by direct entrance of anticancer drugs into cancer cells. This system, named ZnO nanowire-based microbubble generator probe (ZnONW-MGP), is tested on tumorized mice models (by MC4L2 breast cell lines). Mice treated by ZnONW-MGP have ≈82% reduction in tumor size within 10 days with just 25% of conventional dose of paclitaxel while in the absence of the system, they have just a 15% reduction in tumor size. Presence of ZnO nanostructures on microneedles strongly reduces the size of MBs and enhances the efficacy of the sonoporation.