Icotinib-loaded gadolinium metal–organic frameworks as theranostic platforms for combined lung cancer therapy

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Zeino L., Ölçeroğlu B., Tabak E., Sakarya D., Albora A. F., Şenışık A. M., ...Daha Fazla

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, sa.1, ss.1-12, 2027 (SCI-Expanded, Scopus)

Özet

Lung cancer remains the leading cause of cancer-related mortality worldwide, emphasizing the need for multifunctional therapeutic systems with enhanced efficacy and reduced systemic toxicity. In this study, icotinibloaded gadolinium-based metal–organic framework nanostructures (Icotinib/Gd-MOF) were synthesized and evaluated as a theranostic platform combining drug delivery, magnetic resonance imaging (MRI), and radiosensitization capabilities. The synthesized nanostructures were characterized using FT-IR, XRD, TGA, DSC, and SEM analyses. FT-IR and XRD results confirmed successful incorporation of icotinib while preserving the crystalline integrity of the Gd-MOF framework. SEM images revealed morphological changes after drug loading, including partial masking and shortening of nano-needle-like structures. Biological evaluations were performed using A549 lung adenocarcinoma and BEAS-2B healthy bronchial epithelial cells. MTT analyses demonstrated enhanced cytotoxicity of the Icotinib/Gd-MOF formulation against A549 cells compared to free icotinib and bare Gd-MOF. After 72 h treatment, A549 cell viability decreased to nearly 55%, (100 μg/mL) while BEAS-2B cells maintained comparatively higher viability (≈%72). MRI analyses demonstrated enhanced T1-weighted signal intensity in Gd-containing formulations relative to PBS controls. Furthermore, the Icotinib/Gd-MOF formulation exhibited a pronounced dose-dependent therapeutic effect under irradiation conditions, reducing A549 lung cancer cell viability to 41.07 ± 4.32% and 32.02 ± 3.03% following 4 and 8 Gy exposure, respectively, while BEAS-2B healthy epithelial cells maintained comparatively higher viability values of 51.57 ± 4.54% (p < 0.05) and 53.18 ± 3.21% (p < 0.05), indicating enhanced therapeutic selectivity toward cancer cells. Overall, the obtained findings suggest that the developed Icotinib/Gd-MOF system represents a promising multifunctional theranostic nanoplatform for image-guided lung cancer therapy.