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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.

Actin and microtubules form cellular cytoskeletal network, which mediates cell shape, motility and proliferation and are key targets for cancer therapy. Changes in cytoskeletal organization dramatically affect mechanical properties of the cells and correlate with proliferative capacity and invasiveness of cancer cells. Changes in the cytoskeletal network expectedly lead to altered nonmechanical material properties including electrical conductivity as well. Here we applied, for the first time, microtubule and actin based electrical measurement to monitor changes in the electrical properties of breast cancer cells upon administration of antitubulin and anti-actin drugs, respectively. Semiconductive behavior of microtubules and conductive behavior of actins presented different bioelectrical responses (in similar frequencies) of the cells treated by anti-tubulin with respect to anti-actin drugs. Doped silicon nanowires were applied as the electrodes due to their enhanced interactive surface and compatibility with electronic fabrication process. We found that treatment with Mebendazole (MBZ), a microtubule destabilizing agent, decreases electrical resistance while treatment with Paclitaxel (PTX), a microtubule stabilizing agent, leads to an increase in electrical resistance. In contrast, actin destabilizing agents, Cytochalasin D (CytD), and actin stabilizing agent, Phalloidin, lead to an increased and decreased electrical resistance, respectively. Our study thus provides proof-of-principle of the usage of determining the electrical function of cytoskeletal compartments in grading of cancer as well as drug resistance assays.

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Nanocarriers as one of the best strategies to circumvent drug resistance.

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