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

Adv Healthc Mater. 2019 Sep;8(17):e1900613. doi: 10.1002/adhm.201900613. Epub 2019 Jul 22.

Abstract

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.

Keywords: ZnO nanowires; cancer; microbubbles; paclitaxel; sonoporation.

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Cell Line, Tumor
  • Drug Delivery Systems*
  • Female
  • Humans
  • Mice, Inbred BALB C
  • Microbubbles*
  • Nanowires / chemistry
  • Nanowires / ultrastructure
  • Needles*
  • Neoplasm Metastasis
  • Neoplasms / diagnostic imaging*
  • Neoplasms / drug therapy*
  • Ultrasonography*
  • Zinc Oxide / chemistry

Substances

  • Biocompatible Materials
  • Zinc Oxide