Investigation of the Effects of Nanoparticles Containing Irinotecan/TGF-ß Receptor Inhibitor in Colorectal Cancer
BIONANOSCIENCE, cilt.16, sa.8, 2026 (ESCI, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 16 Sayı: 8
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s12668-026-02708-0
- Dergi Adı: BIONANOSCIENCE
- Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, Compendex, EMBASE, INSPEC, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Materials Science & Engineering Collection (ProQuest), Technology Collection (ProQuest)
- İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet
Özet
Colorectal cancer (CRC) treatment with Irinotecan is often limited by dose-dependent toxicity and drug delivery mediated by transforming growth factor-beta (TGF-beta) signaling. Targeting TGF-beta signaling in combination with chemotherapeutic agents using nanoparticle-based delivery systems represents a promising strategy to enhance therapeutic efficacy while minimizing systemic toxicity. In this study, beta-cyclodextrin (beta-CD)-based nanoparticles were synthesized and characterized for the encapsulation and co-delivery of irinotecan and the TGF-beta receptor inhibitor LY2109761. Physicochemical characterization confirmed stable nanoparticle formation with controlled drug loading and release properties. Cytotoxicity analysis demonstrated that Irinotecan-loaded nanoparticles significantly reduced viability of HCT 116 colorectal cancer cells with an IC50 of 91.3 +/- 0.05 & micro;M, representing enhanced efficacy compared to free drug treatment. Importantly, combinatorial nanoparticle treatment further reduced cell viability to 43.6%, indicating improved therapeutic performance at lower drug concentrations. Fluorescence microscopy using propidium iodide staining revealed increased membrane permeability, particularly in the combination treatment group. ELISA analysis showed a moderate decrease in TGF-beta secretion following inhibitor-containing nanoparticle treatment, suggesting partial modulation of tumor survival signaling pathways. In contrast, minimal cytotoxicity was observed in non-cancerous endothelial HUVEC cells, indicating a degree of selectivity toward colorectal cancer cells and suggesting favorable in vitro tolerability of the beta-CD nanoparticle system. These findings suggest that beta-cyclodextrin-based co-delivery of Irinotecan and LY2109761 may enhance cytotoxic activity in colorectal cancer cells and may be associated with modulation of TGF-beta-related signaling. This nanotherapeutic strategy offers an approach for improving CRC treatment efficacy while enabling dose reduction and minimizing off-target toxicity, warranting further in vivo validation.