Epidermal growth factor receptor-targeted sonoporation with microbubbles enhances therapeutic efficacy in a squamous cell carcinoma model

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.

Anticancer effect of novel platinum nanocomposite beads on oral squamous cell carcinoma cells

“…PtNCP beads can also be expected to be used as a drug transport carrier and as an application for improving therapeutic effects. In addition, we have developed the intracellular drug delivery method using ultrasound and cancer specific antibodies‐conjugated microbubbles . Further studies are required to attach PtNCP specifically to cancer cells, developing cancer specific antibodies‐modified PtNCP beads.…”

“…In addition, we have developed the intracellular drug delivery method using ultrasound and cancer specific antibodiesconjugated microbubbles. 15,16 Further studies are required to attach PtNCP specifically to cancer cells, developing cancer specific antibodies-modified PtNCP beads. The strong membranolitic effect of PtNCP beads should make it difficult for the cancer cell to develop resistance to widespread used platinum drugs.…”

“…Our previous study developed in vitro delivery and in vivo transfection systems for bleomycin and the cdtB gene into oral squamous cell carcinoma using sonoporation . In addition, we also have developed anti‐epidermal growth factor receptor antibody‐conjugate microbubbles and evaluated their capacity to enhance anti‐cancer drug cytotoxicity in vitro and in vivo …”

“…15 In addition, we also have developed anti-epidermal growth factor receptor antibody-conjugate microbubbles and evaluated their capacity to enhance anti-cancer drug cytotoxicity in vitro and in vivo. 16 In this study, we evaluated the anticancer effect of the novel platinum nanocomposite beads (PtNCP beads) developed by New Material Development Center in Nippon Steel & Sumikin Chemical Co., Ltd. in vivo and in vitro. It was demonstrated that PtNCP beads dramatically showed cytotoxicity in HSC-3-M3 cells, and tumor growth inhibition in HSC-3-M3 xenografts, with extending histopathological necrosis lesion.…”

Microbubble based sonoporation — from the basics into clinical implications

“…Hirabayashi et al used epidermal growth factor receptor-targeted sonoporation delivery system to deliver bleomycin directly to a squamous cell carcinoma model (mouse tumour xenograft model) obtaining specific binding of EGFR-MBs to Ca9-22 cells that resulted in smaller tumour growth compared with the control group [39].…”