Abstract P3-02-08: Diagnosis, navigation, treatment: A versatile biocompatible and biodegradable mesoporous silica platform of NIR II fluorescence imaging for early diagnosis, breast cancer precisely surgery, and radiosensitization
Authors: Wei Min , Wang Peiyuan , Zhang Guojun 
Published: March 2022

Abstract
Background: Triple-negative breast cancer (TNBC) has the highest recurrence and distant metastasis rates among breast cancer molecular types. In breast-conserving surgery, the insensitivity discrimination of negative margins correlating with locoregional recurrence and poor patient outcomes. As for immunotherapy, only 20 %-40 % of the patients respond to the atezolizumab treatment due to the change of PDL1 receptor. Meanwhile, TNBC has radiotherapy resistance. Novel radiosensitization targets need to be found to enhance both the local and systematic benefits of radiotherapy. Objectives and rationale: We aim to construct an “all in one” multi-functional nanoprobe (MSN-Gd@Aptamer-ICG, NPs) using mesoporous silica as the framework. The mesoporous silica nanospheres are co-doped with gadolinium (Gd3+), loads indocyanine green (ICG) in its mesoporous channel, and conjugates with a specific PDL1 targeting aptamer on the surface. The biocompatible and biodegradable NPs are capable of release ICG by the reaction of intracellular high GSH and tetrasulfide bonds in silica frame. In the diagnosis, NIR II fluorescent imaging of ICG with the high resolution and deep tissue penetration depth screens out PDL1 highly expressed tumors. In surgical resection, it can show a real-time cancerous tissues margin in intraoperative scenarios and the tumors are successfully remove under the navigation of NIR II fluorescent imaging. During metastasis therapy of post-operation, the released Gd3+ effectively deposits X-rays and produces abundant hydroxyl radicals (•OH) and oxidative stress to induce radiosensitizing effects. More importantly, the therapy efficiency is monitored by NIR II fluorescent imaging. Therefore, our multifunctional NPs have roles in the accurate diagnosis of PDL1 expression of tumor in early stage, intraoperative navigation for radical excision, and metastasis eradication with radiosensitization efficiency enhanced, which lays a solid foundation for clinical TNBC therapy. Methods: The probe was 50 nm and it was successfully synthesized and certified. MTT assay suggested that it was nontoxic to normal breast cells and TNBC cells. Transmission Electron Microscope images showed that the probe was stable at the extracellular fluid and was degradable at tumor intracellular conditions. The leaching of ICG and Gd3+ was negligible at the extracellular fluid. The tumor targeting capability of the probe in vitro was evaluated on 4T1 (TNBC, PDL1 low expressed) and MDA-MB-231 (TNBC, PDL1 high expressed) cells by flow cytometry and laser confocal microscope. In vivo, the NIR II fluorescence imaging with a high resolution and tissue penetration depth successfully distinguished 4T1 and MDA-MB-231 bearing mice indicated the superior diagnostic capability of PDL1 via aptamer. In the surgical resection, the NIR II fluorescence imaging of NPs guided to remove the tumor with precisely discriminate the boundary of the tumor. When combined with RT, IHC staining of Ki67 showed that the NPs exhibited superior radiosensitizing effects under NIR II fluorescent imaging guidance in comparison with undoped Gd mesoporous silica nanoprobes. TUNEL fluorescent staining and H&E staining further confirmed that NPs radiation therapy induced more •OH and extensive DNA double-strand breaks. Results and Conclusion: Our biocompatible and biodegradable platform is nontoxic, can screen out PDL1 high expression tumors, and navigate the precise resection in the operation. Besides, it enhances the radioimmunotherapy efficacy of breast metastasis. Our platform is potential to provide new hope for breast cancer diagnostic, guiding resection, and radiosensitization under NIR II fluorescent imaging.
Citation Format: Min Wei, Peiyuan Wang, Guojun Zhang. Diagnosis, navigation, treatment: A versatile biocompatible and biodegradable mesoporous silica platform of NIR II fluorescence imaging for early diagnosis, breast cancer precisely surgery, and radiosensitization [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-08.