Quattrociocchi Claudia, Mangia Alberto, Aime Silvio, Menchise Valeria, Delli Castelli Daniela
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, 10126 Turin, Italy.
CNR (Consiglio Nazionale delle Ricerche), Institute of Biostructures and Bioimaging, Molecular Biotechnology Center, 10126 Turin, Italy.
Pharmaceuticals (Basel). 2023 Sep 14;16(9):1301. doi: 10.3390/ph16091301.
The carbonic anhydrase isoform IX (hCAIX) is one of the main players in extracellular tumor pH regulation, and it is known to be overexpressed in breast cancer and other common tumors. hCA IX supports the growth and survival of tumor cells, and its expression is correlated with metastasis and resistance to therapies, making it an interesting biomarker for diagnosis and therapy. The aim of this work deals with the development of an MRI imaging probe able to target the extracellular non-catalytic proteoglycan-like (PG) domain of CAIX. For this purpose, a specific nanoprobe, LIP_PepC, was designed by conjugating a peptidic interactor of the PG domain on the surface of a liposome loaded with Gd-bearing contrast agents. A Mouse Mammary Adenocarcinoma Cell Line (TS/A) was chosen as an in vitro breast cancer model to test the developed probe. MRI results showed a high selectivity and sensitivity of the imaging probe toward hCAI-expressing TS/A cells. This approach appears highly promising for the in vivo translation of a diagnostic procedure based on the targeting of hCA IX enzyme expression.
碳酸酐酶同工酶IX(hCAIX)是细胞外肿瘤pH调节的主要参与者之一,已知其在乳腺癌和其他常见肿瘤中过表达。hCA IX支持肿瘤细胞的生长和存活,其表达与转移和治疗抗性相关,使其成为诊断和治疗中一个有趣的生物标志物。这项工作的目的是开发一种能够靶向CAIX细胞外非催化蛋白聚糖样(PG)结构域的MRI成像探针。为此,通过将PG结构域的肽类相互作用剂与负载钆造影剂的脂质体表面偶联,设计了一种特异性纳米探针LIP_PepC。选择小鼠乳腺腺癌细胞系(TS/A)作为体外乳腺癌模型来测试所开发的探针。MRI结果显示成像探针对表达hCAI的TS/A细胞具有高选择性和敏感性。这种方法对于基于靶向hCA IX酶表达的诊断程序的体内转化似乎非常有前景。