FOLİK ASİT VE CHELİDONİC ASİT İLE KO-FONKSİYONELİZE EDİLMİŞ GÜMÜŞ NANOPARTİKÜLLER: HELA VE L929 HÜCRELERİNDE FARKLI SİTOTOKSİK VE OKSİDATİF STRES YANITLARI

Abstract

Gümüş nanopartiküller sağlıklı hücrelerde toksisite ve reaktif oksijen türleri (ROS) birikimine neden olmasına rağmen güçlü bir antikanser potansiyel sergilemektedir. Bu çalışmanın amacı, gümüş nanopartiküllerin sağlıklı hücrelerde oluşturduğu toksisiteyi ve ROS aktivitesini azaltırken, kanser hücrelerini seçici olarak hedefleyen bir nanopartikül sistemi geliştirmektir. Bu doğrultuda folik asit (FA) ve chelidonic acid (CA) gümüş nanopartiküllere konjuge edilmiştir. FA, kanser hücrelerinde aşırı eksprese edilen folat reseptörleri aracılığıyla hedeflenmeyi artırarak sitotoksisiteyi güçlendirmiş; CA ise sağlıklı hücrelerde antioksidan kapasiteyi artırarak koruyucu etki sağlamıştır. Böylece çift işlevli bir nanopartikül konjugatı (AgNP/FA/CA) elde edilmiştir. Elde edilen konjugatların fizikokimyasal karakterizasyonu dinamik ışık saçılımı (DLS), taramalı elektron mikroskobu (SEM) ve Fourier dönüşümlü kızılötesi spektroskopi (FT-IR) analizleri ile gerçekleştirilmiştir. DLS sonuçlarına göre AgNP/FA/CA konjugatının hidrodinamik boyutu 178,3 nm, zeta potansiyeli ise −7,5 ± 3,55 mV olarak belirlenmiştir. Partiküllerin kolloidal olarak stabil, monodispers (PDI: 0,1) ve küresel morfolojide olduğu karakterizasyon analizleri ile doğrulanmıştır. FT-IR analizleri, konjugatların FA ve CA ile başarılı şekilde fonksiyonelleştirildiğini göstermiştir. Hücre canlılığı (MTT testi) sonuçlarına göre, AgNP/FA/CA uygulaması L929 fibroblast hücre hattında canlılığı korurken, HeLa kanser hücrelerinde belirgin sitotoksisite oluşturmuştur. Toplam Oksidan Durumu (TOS) ve Toplam Antioksidan Durumu (TAS) verileri kullanılarak hesaplanan Oksidatif Stres İndeksi (OSI) sonuçları, konjugatın hücre tipine bağlı farklı oksidatif stres yanıtları oluşturduğunu göstermiştir. L929 hücrelerinde CA’nın antioksidan etkisiyle OSI değeri kontrol grubunun (118,07) altına düşerek 92,32 olarak belirlenmiş ve hücresel stresin baskılandığı gözlenmiştir. Buna karşılık, HeLa hücrelerinde AgNP/FA/CA konjugatı adaptif antioksidan kapasiteyi aşarak yüksek düzeyde oksidatif stres (OSI: 216,20) indüklemiş ve antitümöral etki göstermiştir. Sonuç olarak AgNP/FA/CA konjugatı, sağlıklı dokularda sistemik toksisiteyi baskılarken kanser hücrelerini seçici olarak hedefleyen, çift işlevli ve potansiyel olarak güvenli bir nanoterapötik yaklaşım sunmaktadır.

Keywords

• Gümüş Nanopartiküller (AgNP'ler)
• Folik Asit (FA)
• Chelidonik Asit (CA)
• Aktif Hedefleme
• Oksidatif Stres.

CO-FUNCTIONALIZED SILVER NANOPARTICLES WITH FOLIC ACID AND CHELIDONIC ACID: DIFFERENTIAL CYTOTOXIC AND OXIDATIVE STRESS RESPONSES IN HELA AND L929 CELLS

Abstract

Silver nanoparticles exhibit strong anticancer potential despite causing toxicity and reactive oxygen species (ROS) accumulation in healthy cells. This study aims to develop a nanoparticle system that selectively targets cancer cells while reducing the toxicity and ROS activity of silver nanoparticles in healthy cells. In this context, folic acid (FA) and chelidonic acid (CA) were conjugated to silver nanoparticles. FA enhanced cytotoxicity by increasing targeting via folate receptors overexpressed in cancer cells, while CA provided a protective effect by increasing antioxidant capacity in healthy cells. Thus, a dual-functional nanoparticle conjugate (AgNP/FA/CA) was obtained. The physicochemical characterization of the obtained conjugates was performed using dynamic light scattering (DLS), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT-IR) analyses. According to DLS results, the hydrodynamic size of the AgNP/FA/CA conjugate was determined to be 178.3 nm, and its zeta potential was −7.5 ± 3.55 mV. Characterization analyses confirmed that the particles were colloidally stable, monodisperse (PDI: 0.1), and spherical in morphology. FT-IR analyses demonstrated that the conjugates were successfully functionalized with FA and CA. According to cell viability (MTT assay) results, the AgNP/FA/CA application maintained viability in the L929 fibroblast cell line, while it caused significant cytotoxicity in HeLa cancer cells. Oxidative Stress Index (OSI) results, calculated using Total Oxidant Status (TOS) and Total Antioxidant Status (TAS) data, showed that the conjugate produced different oxidative stress responses depending on the cell type. In L929 cells, the antioxidant effect of CA caused the OSI value to fall below that of the control group (118.07) to 92.32, indicating that cellular stress was suppressed. In contrast, in HeLa cells, the AgNP/FA/CA conjugate induced high levels of oxidative stress (OSI: 216.20) by exceeding the adaptive antioxidant capacity and exhibited antitumor effects. In conclusion, the AgNP/FA/CA conjugate offers a dual-functional and potentially safe nanotherapeutic approach that selectively targets cancer cells while suppressing systemic toxicity in healthy tissues.

Keywords

• Silver Nanoparticles (AgNPs)
• Folic Acid (FA)
• Chelidonium Acid (CA)
• Active Targeting
• Oxidative Stress.

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