Abstract
Sonoporation is a drug and gene delivery system using ultrasonication that allows the intracellular delivery of foreign molecules that cannot enter cells under normal conditions. We previously reported that sonoporation with microbubbles (MBs) could achieve effective intracellular drug delivery to human gingival squamous carcinoma Ca9-22 cells. In this study, we developed anti-epidermal growth factor receptor (EGFR) antibody-conjugated MBs (EGFR-MBs) and evaluated their capacity to enhance anti-cancer drug toxicity in vitro and in vivo. We first assessed the effect of sonoporation with EGFR-MBs on Ca9-22 cells by the WST-8 assay, flow cytometry and Hoechst’s staining in vitro. Sonoporation and EGFR-MB had a strong cytotoxic effect on Ca9-22 cells with low-dose bleomycin. Furthermore, bleomycin delivery using sonoporation with EGFR-MBs remarkably increased the number of apoptotic cells. We next examined the effect of EGFR-MBs in a murine squamous cell carcinoma model. Bleomycin delivery by sonoporation with EGFR-MBs exhibited remarkable antitumor activity. Together, our results show that EGFR-MBs and ultrasound treatment increases the efficacy and specificity of intracellular drug uptake, suggesting this could be a novel drug-targeting modality for oral squamous cell carcinoma chemotherapy treatment.
Highlights
Medical ultrasound (US) imaging has made remarkable progress in the development of clinical US technology
Our results show that epidermal growth factor receptor (EGFR)-MBs are an effective and specific drug delivery system against cancer cells
We examined the effects on cell proliferation after delivery of BLM by sonoporation using EGFR antibody-conjugated MB (EGFR-MB)
Summary
Medical ultrasound (US) imaging has made remarkable progress in the development of clinical US technology. US creates transient permeability of the cell membrane that enables foreign molecules to enter cells, a process known as sonoporation [2,3].
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