Receptor mediated targeting of EGF-conjugated alginate-PAMAM nanoparticles to lung adenocarcinoma: 2D/3D in vitro and in vivo evaluation

• Published in: International journal of biological macromolecules Vol. 261; no. Pt 1; p. 129758
• Main Authors: Ilhan-Ayisigi, Esra, Saglam-Metiner, Pelin, Sanci, Ebru, Bakan, Buket, Yildirim, Yeliz, Buhur, Aylin, Yavasoglu, Altug, Yavasoglu, N. Ulku Karabay, Yesil-Celiktas, Ozlem
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2024
• Subjects: Adenocarcinoma of Lung - drug therapy; Alginate; Alginates; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Carboplatin; Cell Line, Tumor; Dendrimers; Drug Delivery Systems; Epidermal Growth Factor - metabolism; Female; In vivo lung cancer model; Lung Neoplasms - drug therapy; Microfluidic synthesis; Nanoparticles; PAMAM dendrimer; Targeted drug delivery; Carboplatin; In vivo lung cancer model; Targeted drug delivery; Alginate; PAMAM dendrimer; Microfluidic synthesis
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.129758

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. •Carboplatin loaded into alginate-PAMAM hybrid nanoparticles by microfluidic platform.•EGF conjugation increased the uptake of nanoparticles in both 2D/3D in vitro assays.•EGF-CAP inhibited A549 cell viability compared to Beas-2b at 72 h with a selective manner.•The fluorescence intensity in IVIS spectrum of EGF-CAP treated tumors was much lower.•EGF-CAP induced apoptotic cell death considering the highest TUNEL immunoreactivity.•The in vivo xenograft tumor of BALB/c mice treated with EGF-CAP completely recovered.