Q. Jiang, S. Hao, X. Xiao, and J. Yao contributed equally to this work.
There is an unmet need for specific and sensitive imaging techniques to assess the efficacy of breast cancer therapy, particularly Her-2-expressing cancers. Ultrasonic microbubbles are being developed for use as diagnostic and therapeutic tools. However, nanobubbles circulate longer, are smaller, and diffuse into extravascular tissue to specifically bind target molecules. Here, we characterize a novel Herceptin-conjugated nanobubble for use against Her-2-expressing tumors.
Phospholipid-shelled nanobubbles conjugated with Herceptin (NBs-Her) were fabricated using a thin-film hydration method and characterized in vitro in breast cancer cell lines and in vivo in a mouse model.
The average size of the unconjugated nanobubbles (NBs-Blank) and NBs-Her was 447.1 ± 18.4 and 613.0 ± 25.4 nm, respectively. In cell culture, the NBs-Her adhered to Her-2-positive cells significantly better than to Her-2-negative cells (p < 0.05). In vivo, the peak intensity and the half-time to washout of the NBs-Her were significantly greater than those of the NBs-Blank (p < 0.05). In addition, contrast-enhanced ultrasound imaging quality was improved through the use of the NBs-Her. The nanobubbles were able to penetrate into tumor tissue to allow extravascular imaging, but did not penetrate normal skeletal muscle.
The Herceptin-conjugated nanobubble had many properties that made it useful for in vivo imaging, including longer circulation time and better tumor selectivity. This platform may be able to provide targeted delivery of therapeutic drugs or genes.
Andrulis IL, Bull SB, Blackstein ME, Sutherland D, Mak C, Sidlofsky S, Pritzker KP, et al. Neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group. J Clin Oncol. 1998;16:1340–9. PubMed
Tiwari RK, Borgen PI, Wong GY, Cordon Cardo C, Osborne MP. HER-2/neu amplification and overexpression in primary human breast cancer is associated with early metastasis. Anticancer Res. 1992;12:419–25. PubMed
Buzdar AU, Hortobagyi GN. Recent advances in adjuvant therapy of breast cancer. Semin Oncol. 1999;26:21–7. PubMed
Yin T, Wang P, Zheng R, Zheng B, Cheng D, Zhang X, Shuai X. Nanobubbles for enhanced ultrasound imaging of tumors. Int J Nanomed. 2012;7:895–904.
Subik K, Lee JF, Baxter L, Strzepek T, Costello D, Crowley P, Xing LP, Hung MC, Bonfiglio T, Hicks DG, Tang P. The expression patterns of ER, PR, HER2, CK5/6, EGFR, Ki-67 and AR by immunohistochemical analysis in breast cancer cell lines. Breast Cancer Basic Clin Res. 2010;4:35–41.
- Production and characterization of a novel long-acting Herceptin-targeted nanobubble contrast agent specific for Her-2-positive breast cancers
- Springer Japan
Neu im Fachgebiet Chirurgie
Mail Icon II