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Receptor mediated targeting of EGF-conjugated alginate-PAMAM nanoparticles to lung adenocarcinoma: 2D/3D in vitro and in vivo evaluation      
Yazarlar
Esra Ilhan-Ayisigi
Kırşehir Ahi Evran Üniversitesi, Turkey
Pelin Saglam-Metiner
Ege University Faculty of Engineering, Turkey
Ebru Sanci
Ege Üniversitesi, Turkey
Buket Bakan
Atatürk Üniversitesi, Turkey
Yeliz Yildirim
Ege Üniversitesi, Turkey
Aylin Buhur
Ege University Medical School, Turkey
Altug Yavasoglu
Ege University Medical School, Turkey
N. Ulku Karabay Yavasoglu
Ege Üniversitesi, Turkey
Ozlem Yesil-Celiktas
Ege University Faculty of Engineering, Turkey
Özet
Carboplatin (cis-diamine (1,1-cyclobutandicarboxylaso)‑platinum (II)) is a second-generation antineoplastic drug, which is widely used for chemotherapy of lung, colon, breast, cervix, testicular and digestive system cancers. Although preferred over cisplatin due to the lower incidence of nephrotoxicity and ototoxicity, efficient carboplatin delivery remains as a major challenge. In this study, carboplatin loaded alginate- poly(amidoamine) (PAMAM) hybrid nanoparticles (CAPs) with mean sizes of 192.13 ± 4.15 nm were synthesized using a microfluidic platform, then EGF was conjugated to the surface of CAPs (EGF-CAPs) for the receptor-targeted delivery. Hence, increased FITC+ cell counts were observed in A549 spheroids after EGF-CAP treatment compared to CAP in the 3D cellular uptake study. As such, the cytotoxicity of EGF-CAP was approximately 2-fold higher with an IC50 value of 35.89 ± 10.37 μg/mL compared to the CAPs in A549 spheroids. Based on in vivo experimental animal model, anti-tumor activities of the group treated with CAP decreased by 61 %, whereas the group treated with EGF-CAP completely recovered. Additionally, EGF-CAP application was shown to induce apoptotic cell death. Our study provided a new strategy for designing a hybrid nanoparticle for EGFR targeted carboplatin delivery with improved efficacy both in vitro and in vivo applications.
Anahtar Kelimeler
Alginate | Carboplatin | In vivo lung cancer model | Microfluidic synthesis | PAMAM dendrimer | Targeted drug delivery
Makale Türü Özgün Makale
Makale Alt Türü SCOPUS dergilerinde yayımlanan tam makale
Dergi Adı International Journal of Biological Macromolecules
Dergi ISSN 0141-8130
Makale Dili İngilizce
Basım Tarihi 03-2024
Cilt No 261
Sayı 1
Doi Numarası 10.1016/j.ijbiomac.2024.129758