Abstract P1-01-04: Uptake of trastuzumab targeted mesoporous silica-coated chitosan capped gold nanorods in breast cancer cell lines and <i>ex vivo</i> patient samples
Authors: Akiko Chiba, Alexandra Thomas, Karl N. Thomas, Abhilash Samykutty, Molly McNally, Lacey McNally
Journal: Cancer Research (2020)

Abstract Background: Approximately two-thirds of operative breast cancer cases are suitable for breast conserving surgery (BCS). In order for BCS to be successful, negative surgical margins should be obtained. Despite improvement in imaging techniques, the ability to achieve negative margins for BCS remains variable with positive margin rates ranging from 21 to 50%. Due to this high re-excision rate, there is an unmet need for a reliable technology to localize the tumor and assess excision margins in real time. Multispectral Optoacoustic Tomography (MSOT) is an emerging imaging modality capable of real time imaging of numerous contrast agents with enhanced spatial resolution of 75µm at depths of 5 cm. This imaging modality has the ability to visualize tumor tissue in a standard operating room setting allowing for precise surgical excision with the potential of increasing rate of negative margins. We developed gold nanorods targeting Human epidermal growth factor receptor-2 (HER2) as a contrast agent to visualize the breast tumor tissue in cell line as well as in ex vivo patient samples using MSOT. Methods: Gold nanorods were created using hydrogen peroxide (GNR-H2O2) as a reducing agent to create an MSOT detectable contrast agent; the nanorods were stabilized via encapsulation with mesoporous silica together with subsequent chitosan capping. HER2+ breast cancer cells were specifically targeted by conjugating the mesoporous silica-coated chitosan capped gold nanorods (CMGs) to Trastuzumab resulting in TRA-CMG particles. The TRA-CMG particles were evaluated in HER2+ and HER2- breast cancer cell lines as well as fresh HER2+ (N=6) and HER2- freshly resected patient tumor tissues (N=6). All HER2- tumor samples were triple negative breast cancer (TNBC) subtype. Tumor uptake was evaluated in tissue mimicking phantoms using MSOT. In vivo, TRA-CMG were IV injected into female mice with DY36T2Q tumors and imaged using MSOT imaging 6 hours post injection (N=5). Results: TRA-CMG particles were 8nm wide and 98nm in length. Treatment of HER2+ breast cancer cell lines, DY36T2Q and SKBR3, with TRA-CMG resulted in 2.5x and 3.1x enhanced signal, respectively, as compared to HER2- MDA-MD468 cells (p&amp;lt;0.01). In ex vivo patient samples treated with TRA-CMG that were placed into tissue mimicking phantoms and imaged using MSOT, TRA-CMG had 12x greater uptake in HER2+ samples than in HER2- samples (p&amp;lt;0.004) (Table) In vivo evaluation of TRA-CMG demonstrated tumor specific uptake with 12.1 a.u, compared to liver 1.1 a.u., and kidney 0.9 a.u. in the DY36T2Q breast cancer mode (p&amp;lt;0.007). Conclusion: The significant uptake of TRA-CMG particles in HER2+ tumors suggests the potential of this particle to be used for diagnostic imaging as well as with intraoperative imaging using MSOT. Future clinical applications include improving the rate of negative margins for patients undergoing breast conservation. Patient tumor chracteristics and TRC-CMG uptakePatientBreast Cancer SubtypeTumor GradePathologic StageTRA-CMG Uptake (a.u.)1TNBC3ypT3N3a1.22TNBC3ypT2N00.33TNBC3ypT4bN1a0.54ER+PR+HER2+2pT1cN213.35ER+PR-HER2+3pT1cN017.96TNBC2ypT0N00.47ER-PR-HER2+3pT2N019.48ER+PR-HER2+3pT2N015.69ER-PR-HER2+3pT1cN016.610TNBC3pT2N1a0.911ER+PR+HER2+3ypTN018.712TNBC2pT1cN00.7 Citation Format: Akiko Chiba, Alexandra Thomas, Karl N. Thomas, Abhilash Samykutty, Molly McNally, Lacey McNally. Uptake of trastuzumab targeted mesoporous silica-coated chitosan capped gold nanorods in breast cancer cell lines and ex vivo patient samples [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-01-04.