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Updated: Jun 24, 2025
Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
Surface-engineered erythrocyte membrane-camouflage fluorescent bioprobe for precision ovarian cancer surgery
Zijuan Meng1, Hanzhi Ouyang1, Yuxin Hu1
1Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China.
Purpose:
Fluorescence imaging-guided surgery has been used in oncology. However, for tiny tumors, the current imaging probes are still difficult to achieve high-contrast imaging, leading to incomplete resection. In this study, we achieved precise surgical resection of tiny metastatic cancers by constructing an engineering erythrocyte membrane-camouflaged bioprobe (AR-M@HMSN@P).
Methods:
AR-M@HMSN@P combined the properties of aggregation-induced emission luminogens (AIEgens) named PF3-PPh3 (P), with functional erythrocyte membrane modified by a modular peptide (AR). Interestingly, AR was composed of an asymmetric tripodal pentapeptide scaffold (GGKGG) with three appended modulars: KPSSPPEE (A6) peptide, RRRR (R4) peptide and cholesterol. To verify the specificity of the probe in vitro, SKOV3 cells with overexpression of CD44 were used as the positive group, and HLF cells with low expression of CD44 were devoted as the control group. The AR-M@HMSN@P fluorescence imaging was utilized to provide surgical guidance for the removal of micro-metastatic lesions.
Results:
In vivo, the clearance of AR-M@HMSN@P by the immune system was reduced due to the natural properties inherited from erythrocytes. Meanwhile, the A6 peptide on AR-M@HMSN@P was able to specifically target CD44 on ovarian cancer cells, and the electrostatic attraction between the R4 peptide and the cell membrane enhanced the firmness of this targeting. Benefiting from these multiple effects, AR-M@HMSN@P achieved ultra-precise tumor imaging with a signal-to-noise ratio (SNR) of 15.2, making it possible to surgical resection of tumors < 1 mm by imaging guidance.
Conclusion:
We have successfully designed an engineered fluorescent imaging bioprobe (AR-M@HMSN@P), which can target CD44-overexpressing ovarian cancers for precise imaging and guide the resection of minor tumors. Notably, this work holds significant promise for developing biomimetic probes for clinical imaging-guided precision cancer surgery by exploiting their externally specified functional modifications.
Insights
A novel engineered bioprobe, AR-M@HMSN@P, enables high-contrast fluorescence imaging for precise surgical resection of tiny metastatic cancers. This biomimetic probe targets CD44-overexpressing ovarian tumors, improving surgical outcomes.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanotechnology
Background:
- Fluorescence imaging-guided surgery is crucial in oncology.
- Current probes struggle with high-contrast imaging of tiny tumors, leading to incomplete resection.
Purpose of the Study:
- To develop an engineered erythrocyte membrane-camouflaged bioprobe (AR-M@HMSN@P) for precise surgical resection of tiny metastatic cancers.
Main Methods:
- Constructed AR-M@HMSN@P by combining aggregation-induced emission luminogens (AIEgens) with erythrocyte membrane modified by a modular peptide (AR).
- AR peptide includes A6 peptide, R4 peptide, and cholesterol for targeting CD44-overexpressing SKOV3 cells.
- Utilized AR-M@HMSN@P fluorescence imaging for surgical guidance of micro-metastatic lesions.
Main Results:
- AR-M@HMSN@P exhibited reduced immune clearance due to erythrocyte properties.
- Specific targeting of CD44 on ovarian cancer cells via A6 peptide and enhanced by R4 peptide.
- Achieved ultra-precise tumor imaging with a signal-to-noise ratio (SNR) of 15.2 for resecting tumors <1 mm.
Conclusions:
- Successfully designed AR-M@HMSN@P for precise imaging and resection of minor CD44-overexpressing ovarian tumors.
- This biomimetic probe shows promise for clinical imaging-guided precision cancer surgery.
