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Published on: February 3, 2015
An activated excretion-retarded tumor imaging strategy towards metabolic organs
Da-Yong Hou1,2,3, Man-Di Wang3,4, Xing-Jie Hu3,5
1Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, Harbin, 150001, China.
Abstract:
Intraoperative fluorescence-based tumor imaging plays a crucial role in performing the oncological safe tumor resection with the advantage of differentiating tumor from normal tissues. However, the application of these fluorescence contrast agents in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) was dramatically hammered as a result of lacking active targeting and poor retention time in tumor, which limited the Signal to Noise Ratio (SNR) and narrowed the imaging window for complicated surgery. Herein, we reported an activated excretion-retarded tumor imaging (AERTI) strategy, which could be in situ activated with MMP-2 and self-assembled on the surface of tumor cells, thereby resulting in a promoted excretion-retarded effect with an extended tumor retention time and enhanced SNR. Briefly, the AERTI strategy could selectively recognize the Integrin αvβ3. Afterwards, the AERTI strategy would be activated and in situ assembled into nanofibrillar structure after specifically cleaved by MMP-2 upregulated in a variety of human tumors. We demonstrated that the AERTI strategy was successfully accumulated at the tumor sites in the 786-O and HepG2 xenograft models. More importantly, the modified modular design strategy obviously enhanced the SNR of AERTI strategy in the imaging of orthotopic RCC and HCC. Taken together, the results presented here undoubtedly confirmed the design and advantage of this AERTI strategy for the imaging of tumors in metabolic organs.
Insights
A novel activated excretion-retarded tumor imaging (AERTI) strategy enhances tumor visualization during surgery. This approach improves signal-to-noise ratio and retention time for better tumor resection in renal cell carcinoma and hepatocellular carcinoma.
Area of Science:
- Biomedical imaging
- Nanotechnology
- Oncology
Background:
- Intraoperative fluorescence imaging aids tumor resection but faces limitations in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC).
- Existing contrast agents lack active targeting and have short tumor retention, reducing signal-to-noise ratio (SNR) and imaging windows.
Purpose of the Study:
- To develop an activated excretion-retarded tumor imaging (AERTI) strategy for improved intraoperative visualization of RCC and HCC.
- To enhance tumor-specific targeting, retention time, and SNR for safer oncological surgeries.
Main Methods:
- Developed AERTI strategy with in situ activation by MMP-2 and self-assembly on tumor cell surfaces.
- Engineered AERTI to selectively recognize Integrin αvβ3 and assemble into nanofibrillar structures upon MMP-2 cleavage.
- Evaluated AERTI accumulation and imaging performance in 786-O and HepG2 xenograft and orthotopic models.
Main Results:
- AERTI strategy demonstrated successful accumulation at tumor sites in both RCC and HCC models.
- The modular design significantly enhanced the SNR of AERTI for orthotopic RCC and HCC imaging.
- Achieved promoted excretion-retarded effect with extended tumor retention time and improved SNR.
Conclusions:
- The AERTI strategy offers an effective approach for intraoperative tumor imaging in metabolic organs.
- This strategy overcomes limitations of existing agents by improving targeting, retention, and SNR.
- Confirmed the design advantages of AERTI for enhanced visualization in complex oncological surgeries.
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