Hybrid Biosilica Nanoparticles for in-vivo Targeted Inhibition of Colorectal Cancer Growth and Label-Free Imaging

Abstract

Donatella Delle Cave,1,* Maria Mangini,2,* Chiara Tramontano,3,* Luca De Stefano,3 Marco Corona,1 Ilaria Rea,3 Anna Chiara De Luca,2 Enza Lonardo1 1National Research Council, Institute of Genetics and Biophysics, Naples, 80131, Italy; 2National Research Council, Institute for Experimental Endocrinology and Oncology “G. Salvatore”, Second Unit, Naples, 80131, Italy; 3National Research Council, Institute of Applied Sciences and Intelligent Systems, Unit of Naples, Naples, 80131, Italy*These authors contributed equally to this workCorrespondence: Ilaria Rea; Anna Chiara De Luca, Email [email protected]; [email protected]: 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.Keywords: targeted drug delivery, Raman imaging, antibody quantification, biosilica nanoparticle, in vivo treatment, colorectal cancer

Keywords

• targeted drug delivery
• raman imaging
• antibody quantification
• biosilica nanoparticle
• in vivo treatment
• colorectal cancer