Higbee-Dempsey Elizabeth, Amirshaghaghi Ahmad, Case Matthew J, Miller Joann, Busch Theresa M, Tsourkas Andrew
Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Adv Ther (Weinh). 2019 Sep;2(9). doi: 10.1002/adtp.201900088. Epub 2019 Jul 26.
Traditional oncology treatment modalities are often associated with a poor therapeutic index. This has driven the development of new targeted treatment modalities, including several based on the conversion of optical light into heat energy (photothermal therapy, PTT) and sound waves (photoacoustic imaging, PA) that can be applied locally. These approaches are especially effective when combined with photoactive nanoparticles that preferentially accumulate in tissues of interest and thereby further increase spatiotemporal resolution. In this study, two clinically-used materials that have proven effective in both PTT and PA - indocyanine green and gold nanoparticles - were combined into a single nanoformulation. These particles, "ICG-AuNP clusters", incorporated high concentrations of both moieties without the need for additional stabilizing or solubilizing reagents. The clusters demonstrated high theranostic efficacy both and , compared with ICG alone. Specifically, in an orthotopic mouse model of triple-negative breast cancer, ICG-AuNP clusters could be injected intravenously, imaged in the tumor by PA, and then combined with near-infrared laser irradiation to successfully thermally ablate tumors and prolong animal survival. Altogether, this novel nanomaterial demonstrates excellent therapeutic potential for integrated treatment and imaging.
传统的肿瘤治疗方式往往伴随着较差的治疗指数。这推动了新的靶向治疗方式的发展,包括几种基于将光转化为热能(光热疗法,PTT)和声波(光声成像,PA)的局部应用方法。当与优先在感兴趣的组织中积累从而进一步提高时空分辨率的光活性纳米颗粒结合使用时,这些方法特别有效。在本研究中,两种已在PTT和PA中均证明有效的临床使用材料——吲哚菁绿和金纳米颗粒——被组合成单一的纳米制剂。这些颗粒,即“ICG-AuNP簇”,无需额外的稳定剂或增溶剂即可掺入高浓度的两种成分。与单独的吲哚菁绿相比,这些簇在体内和体外均表现出高的诊疗效果。具体而言,在三阴性乳腺癌的原位小鼠模型中,ICG-AuNP簇可以静脉注射,通过PA在肿瘤中成像,然后结合近红外激光照射成功地热消融肿瘤并延长动物存活时间。总之,这种新型纳米材料展示了用于综合治疗和成像的优异治疗潜力。