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A pH ratiometrically responsive surface enhanced resonance Raman scattering probe for tumor acidic margin delineation
Wenjia Duan1, Qi Yue2, Ying Liu3
1Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University Shanghai 201203 China congli@fudan.edu.cn.
Abstract:
Surgery remains the mainstay for most solid tumor treatments. However, surgeons face challenges in intra-operatively identifying invasive tumor margins due to their infiltrative nature. Incomplete excision usually leads to early recurrence, while aggressive resection may injure adjacent functional tissues. Herein, we report a pH responsive ratiometric surface-enhanced Raman scattering (SERRS) probe that determined physiological pHs with a high sensitivity and tissue penetration depth via an innovative mechanism named spatial orientation induced intramolecular energy transfer (SOIET). Due to the positive correlation between tumor acidity and malignancy, an acidic margin-guided surgery strategy was implemented in live animal models by intra-operatively assessing tissue pH/malignancy of the suspicious tissues in tumor cutting edges. This surgery remarkably extended the survival of animal models and minimized their post-surgical complications, showing promise in precisely identifying invasive tumor boundaries and achieving a balance between maximum tumor debulking and minimal functional impairment.
Insights
A novel pH-responsive surface-enhanced Raman scattering (SERRS) probe aids surgeons in identifying invasive tumor margins during surgery. This new method improves tumor removal accuracy, extending survival and reducing complications in animal models.
Area of Science:
- Biomedical Engineering
- Surgical Oncology
- Chemical Sensing
Background:
- Identifying invasive tumor margins during surgery is challenging due to infiltrative growth.
- Incomplete tumor excision leads to recurrence, while overly aggressive resection can damage healthy tissues.
Purpose of the Study:
- To develop a pH-responsive ratiometric surface-enhanced Raman scattering (SERRS) probe for intra-operative margin assessment.
- To implement an acidic margin-guided surgery strategy using the SERRS probe to improve surgical outcomes.
Main Methods:
- A novel pH-responsive ratiometric SERRS probe utilizing spatial orientation induced intramolecular energy transfer (SOIET) was developed.
- The probe was used to assess tissue pH and malignancy in real-time during surgery in live animal models.
- A surgical strategy guided by acidic tumor margins was implemented.
Main Results:
- The SERRS probe demonstrated high sensitivity and tissue penetration depth for physiological pH determination.
- Intra-operative assessment of suspicious tissue pH at tumor cutting edges was achieved.
- Acidic margin-guided surgery significantly extended survival and minimized post-surgical complications in animal models.
Conclusions:
- The developed SERRS probe and acidic margin-guided surgery strategy show promise for precise identification of invasive tumor boundaries.
- This approach can help achieve a balance between maximizing tumor removal and minimizing damage to adjacent functional tissues.
- This technology has the potential to improve surgical precision and patient outcomes in solid tumor treatment.

