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Hybrid Biosilica Nanoparticles for in-vivo Targeted Inhibition of Colorectal Cancer Growth and Label-Free Imaging
Donatella Delle Cave1, Maria Mangini2, Chiara Tramontano3
1National Research Council, Institute of Genetics and Biophysics, Naples, 80131, Italy.
Background:
Metastasis-initiating cells are key players in progression, resistance, and relapse of colorectal cancer (CRC), by leveraging the regulatory relationship between Transforming Growth Factor-beta (TGF-β) signaling and anti-L1 cell adhesion molecule (L1CAM).
Methods:
This study introduces a novel strategy for CRC targeted therapy and imaging based on the use of a hybrid nanosystem made of gold nanoparticles-covered porous biosilica further modified with the (L1CAM) antibody.
Results:
The nanosystem intracellularly delivers galunisertib (LY), a TGF-β inhibitor, aiming to inhibit epithelial-mesenchymal transition (EMT), a process pivotal for metastasis. Anti-L1CAM antibody-functionalized nanoparticles (NPs) target tumor-initiating cells expressing L1CAM, inhibiting cancer growth. The number of antibody molecules conjugated to the single NP is precisely quantified, revealing a high surface coverage that facilitates the tumor targeting. The therapeutic efficacy of the nanosystem is investigated in organoid-like cultures of CRC cells and in vivo mouse models, showing a significant reduction in tumor growth. The spatial distribution of NPs within CRC tumors from mice is investigated using a label-free optical approach based on Raman micro-spectroscopy.
Conclusion:
This research highlights the multifunctional capabilities of engineered biosilica NPs, which offer new insights in targeted CRC therapy and imaging, improving patient outcomes and paving the way for personalized therapies.
Insights
This study developed a novel nanosystem to target metastasis-initiating cells in colorectal cancer (CRC). The system delivers a TGF-β inhibitor, significantly reducing tumor growth and offering new avenues for CRC therapy and imaging.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Metastasis-initiating cells drive colorectal cancer (CRC) progression, resistance, and relapse.
- These cells exploit the interplay between Transforming Growth Factor-beta (TGF-β) signaling and L1 cell adhesion molecule (L1CAM).
Purpose of the Study:
- To develop a novel hybrid nanosystem for targeted CRC therapy and imaging.
- To inhibit epithelial-mesenchymal transition (EMT) and target tumor-initiating cells.
Main Methods:
- A hybrid nanosystem composed of gold nanoparticles-covered porous biosilica functionalized with an anti-L1CAM antibody was engineered.
- The nanosystem delivers galunisertib (LY), a TGF-β inhibitor, to inhibit EMT.
- Nanoparticle (NP) surface coverage and therapeutic efficacy were evaluated in CRC organoid cultures and mouse models.
- Raman micro-spectroscopy was used to investigate NP distribution in vivo.
Main Results:
- The nanosystem demonstrated high surface coverage of anti-L1CAM antibodies for effective tumor targeting.
- Significant reduction in tumor growth was observed in both organoid and in vivo models.
- The study quantified antibody conjugation, confirming high surface coverage for enhanced tumor targeting.
Conclusions:
- Engineered biosilica NPs possess multifunctional capabilities for targeted CRC therapy and imaging.
- This approach provides new insights for improving CRC patient outcomes.
- The research paves the way for personalized therapeutic strategies in CRC.
