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Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
Surface-enhanced resonance Raman scattering nanostars for high-precision cancer imaging
Stefan Harmsen1, Ruimin Huang2, Matthew A Wall3
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Abstract:
The inability to visualize the true extent of cancers represents a significant challenge in many areas of oncology. The margins of most cancer types are not well demarcated because the cancer diffusely infiltrates the surrounding tissues. Furthermore, cancers may be multifocal and characterized by the presence of microscopic satellite lesions. Such microscopic foci represent a major reason for persistence of cancer, local recurrences, and metastatic spread, and are usually impossible to visualize with currently available imaging technologies. An imaging method to reveal the true extent of tumors is desired clinically and surgically. We show the precise visualization of tumor margins, microscopic tumor invasion, and multifocal locoregional tumor spread using a new generation of surface-enhanced resonance Raman scattering (SERRS) nanoparticles, which are termed SERRS nanostars. The SERRS nanostars feature a star-shaped gold core, a Raman reporter resonant in the near-infrared spectrum, and a primer-free silication method. In genetically engineered mouse models of pancreatic cancer, breast cancer, prostate cancer, and sarcoma, and in one human sarcoma xenograft model, SERRS nanostars enabled accurate detection of macroscopic malignant lesions, as well as microscopic disease, without the need for a targeting moiety. Moreover, the sensitivity (1.5 fM limit of detection) of SERRS nanostars allowed imaging of premalignant lesions of pancreatic and prostatic neoplasias. High sensitivity and broad applicability, in conjunction with their inert gold-silica composition, render SERRS nanostars a promising imaging agent for more precise cancer imaging and resection.
Insights
New SERRS nanostars precisely visualize cancer margins and microscopic spread, improving detection of both macroscopic and premalignant lesions in various cancer models. This breakthrough offers enhanced precision for cancer imaging and surgical resection.
Area of Science:
- Oncology
- Nanotechnology
- Medical Imaging
Background:
- Accurate visualization of cancer extent is crucial for effective treatment and surgical planning.
- Diffuse infiltration, multifocality, and microscopic satellite lesions present significant challenges for current imaging technologies.
- Existing methods often fail to detect microscopic disease, leading to cancer persistence and recurrence.
Purpose of the Study:
- To develop and evaluate a novel imaging agent for precise visualization of tumor margins and microscopic cancer spread.
- To assess the efficacy of SERRS nanostars in detecting both macroscopic and microscopic malignant and premalignant lesions.
- To demonstrate the broad applicability of SERRS nanostars across different cancer types.
Main Methods:
- Development of SERRS nanostars with a gold core, near-infrared Raman reporter, and silication.
- In vivo testing in genetically engineered mouse models of pancreatic, breast, prostate cancer, and sarcoma.
- Evaluation in a human sarcoma xenograft model.
- Assessment of sensitivity and detection limits.
Main Results:
- SERRS nanostars enabled precise visualization of tumor margins, microscopic invasion, and multifocal spread.
- Accurate detection of macroscopic and microscopic disease was achieved across multiple cancer models without targeting moieties.
- Ultra-high sensitivity (1.5 fM limit of detection) allowed imaging of premalignant lesions.
Conclusions:
- SERRS nanostars represent a promising new imaging agent for precise cancer detection.
- Their high sensitivity, broad applicability, and inert composition support their use in improved cancer imaging and surgical resection.
- This technology has the potential to significantly impact oncology by enabling earlier and more accurate diagnosis.
