Journal
ACS NANO
Volume 12, Issue 8, Pages 7974-7985Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b02681
Keywords
nanomedicine; gap-enhanced Raman tag; cancer theranostics; residual microtumors; surface-enhanced Raman spectroscopy
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Funding
- National Natural Science Foundation of China [81471779, 31671003, 81741014, 21375087, 81571763, 81622026]
- Thousand Young Talents Program
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning [TP2014028]
- Shanghai Jiao Tong University [YG2016MS51, YG2017MS54]
- Shanghai Key Laboratory of Gynecologic Oncology
- Shanghai Jiao Tong University School of Medicine [BXJ201704]
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The inability to intraoperatively diagnose and eliminate microscopic residual tumors represents a significant challenge in cancer surgery. These residual microtumors cause lethal recurrence and metastasis. Herein, we show a crucial example of Raman imaging with gap-enhanced Raman tags (GERTs) to serve as a robust platform for intraoperative detection and eradication of residual microscopic foci, which exist in surgical margins, tumor invasion, and multifocal tumor spread. The GERTs feature gap-enhanced gold core-shell nanostructures, with Raman reporters embedding inside the interior gap junction. This nanostructure elicits highly sensitive and photostable Raman signals for microtumor detection by applying a 785 nm, low-energy laser and produces hyperthermia effects for microtumor ablation upon switching a 808 nm, high-power laser. In the orthotopic prostate metastasis tumor model, systematic delivery of GERTs enabled precise imaging and real-time ablation of macroscopic malignant lesions around the surgical bed without damaging normal tissues. Consequently, the GERTs-based surgery prevented local recurrence and delivered 100% tumor-free survival. These results suggest the efficiency of theranostic GERTs for precise detection and removal of residual miroctumors, broadening the avenues to apply Raman-based imaging for theranostic precision medicine.
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