Solomonov Inna, Locatelli Irene, Tortorella Silvia, Unni Manu, Aharoni Shay-Lee, Alchera Elisa, Locatelli Erica, Maturi Mirko, Venegoni Chiara, Lucianò Roberta, Salonia Andrea, Corti Angelo, Curnis Flavio, Grasso Valeria, Malamal Gayathri, Jose Jithin, Comes Franchini Mauro, Sagi Irit, Alfano Massimo
Department of Immunology and Regenerative Biology, Weizmann Institute of Science Rehovot 76100 Israel
Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele Milan Italy
Nanoscale Adv. 2024 Jun 7;6(14):3655-3667. doi: 10.1039/d4na00204k. eCollection 2024 Jul 9.
Fibrillar collagen accumulation emerges as a promising biomarker in several diseases, such as desmoplastic tumors and unstable atherosclerotic plaque. Gold nanorods (GNRs) hold great potential as contrast agents in high-resolution, biomedically safe, and non-invasive photoacoustic imaging (PAI). This study presents the design and characterization of a specialized imaging tool which exploits GNR assisted targeted photoacoustic imaging that is tailored for the identification of fibrillar collagen. In addition to the photoacoustic characterization of collagen in the NIR 1 and 2 regions, we demonstrate the detailed steps of conjugating a decoy to GNRs. This study serves as a proof of concept, that demonstrates that conjugated collagenase-1 (MMP-1) generates a distinct and collagen-specific photoacoustic signal, facilitating real-time visualization in the wavelength range of 700-970 nm (NIR I). As most of the reported studies utilized the endogenous contrast of collagen in the NIR II wavelength that has major limitations to perform deep tissue imaging, the approach that we are proposing is unique and it highlights the promise of MMP-1 decoy-functionalized GNRs as novel contrast agents for photoacoustic imaging of collagen in the NIR 1 region. To our knowledge this is the first time functionalized GNRs are optimized for the detection of fibrillar collagen and utilized in the field of non-invasive photoacoustic imaging that can facilitate a better prognosis of desmoplastic tumors and broken atherosclerotic plaques.
在几种疾病中,如促结缔组织增生性肿瘤和不稳定动脉粥样硬化斑块,纤维状胶原蛋白积累已成为一种很有前景的生物标志物。金纳米棒(GNRs)作为高分辨率、生物医学安全且无创的光声成像(PAI)造影剂具有巨大潜力。本研究介绍了一种专门成像工具的设计与特性,该工具利用GNR辅助靶向光声成像,针对纤维状胶原蛋白的识别进行了定制。除了对近红外1区和2区胶原蛋白进行光声特性分析外,我们还展示了将诱饵与GNRs偶联的详细步骤。本研究作为概念验证,表明偶联的胶原酶-1(MMP-1)产生独特且特定于胶原蛋白的光声信号,便于在700 - 970 nm(近红外I)波长范围内进行实时可视化。由于大多数已报道的研究利用近红外II波长下胶原蛋白的内源性对比度,这在进行深部组织成像时有很大局限性,我们提出的方法是独特的,它突出了MMP-1诱饵功能化的GNRs作为近红外1区胶原蛋白光声成像新型造影剂的前景。据我们所知,这是首次将功能化的GNRs优化用于检测纤维状胶原蛋白,并应用于无创光声成像领域,这有助于对促结缔组织增生性肿瘤和破裂的动脉粥样硬化斑块做出更好的预后判断。