Tuning Cisplatin–Graphene Interactions: The Impact of Dopant Identity and Concentration

Öz

Cisplatin remains a cornerstone of cancer therapy, yet its efficacy is compromised by severe toxicity and off-target uptake, driving the search for targeted delivery systems such as graphene-based nanocarriers. Despite the promise of heteroatom doping to enhance drug loading, a detailed mechanistic understanding of how dopant identity and concentration alter the delicate balance of noncovalent forces is lacking. This study aims to elucidate the atomic-level drivers of cisplatin physisorption on boron- and nitrogen-doped graphene nano-fragments. Using dispersion-corrected density functional theory (PBE-D3(BJ)) coupled with energy decomposition analysis via DFT-SAPT, this study reveals that moderate doping significantly strengthens adsorption. Specifically, boron dopants enhance binding through electrostatic complementarity, whereas nitrogen dopants primarily increase polarization and induction effects. However, a key finding is that higher dopant loadings lead to an "electronic smoothing" of the surface potential, unexpectedly weakening the binding affinity. These results suggest a practical "doping window" of 5–8% as an optimal design strategy for engineering graphene carriers with strong yet controlled drug retention.

Anahtar Kelimeler

• Cisplatin
• Graphene nanocarriers
• Heteroatom doping
• Drug delivery

Sisplatin-Grafen Etkileşiminin Modülasyonu: Katkı Türü ve Konsantrasyonun Etkisi

Öz

Sisplatin, kanser tedavisinin temel taşlarından biri olma özelliğini korumakla birlikte; etkinliği, ciddi toksisite ve hedef dışı etki sorunları nedeniyle gölgelenmektedir. Bu durum, grafen tabanlı nanotaşıyıcılar gibi hedeflendirilmiş iletim sistemlerine yönelik arayışı tetiklemektedir. Heteroatom katkılama işlemi grafenin ilaç taşınım potansiyelini artırmasına rağmen; katkı maddesinin kimliği ve konsantrasyonunun, kovalent olmayan kuvvetlerin dengesini ne yönde değiştirdiği henüz tam olarak anlaşılamamıştır. Bu çalışma, sisplatinin bor ve azot katkılı grafen nano-parçacıkları ile etkileşimini atomik düzeyde yönlendiren etkileri aydınlatmayı amaçlamaktadır. DFT-SAPT analizleri ile desteklenen ve dispersiyon düzeltmeli yoğunluk fonksiyonel teorisi (PBE-D3(BJ)) kullanılarak gerçekleştirilen bu çalışma, %5-8 oranındaki ılımlı katkılamanın adsorpsiyonu belirgin şekilde güçlendirdiğini ortaya koymaktadır. Özellikle bor katkısı elektrostatik çekim kuvveti üzerinden bağlanmayı artırırken, azot katkısı ağırlıklı olarak polarizasyon ve indüksiyon etkilerini yükseltmektedir. Bununla birlikte çalışmanın en çarpıcı bulgusu, yüksek dopant oranlarının grafen yüzey potansiyelinde bir 'elektronik pürüzsüzleşmeye' (electronic smoothing) yol açarak, bağlanma afinitesini beklenmedik bir şekilde zayıflatmasıdır. Elde edilen sonuçlar, güçlü ve kontrollü ilaç tutulumuna sahip grafen taşıyıcıların tasarlanmasında, %5-8 aralığındaki bir 'katkılama penceresinin' en uygun strateji olduğunu göstermektedir.

Anahtar Kelimeler

• Sisplatin
• Grafen nanotaşıyıcılar
• Heteroatom katkılama
• İlaç taşınımı
• Kovalent olmayan etkileşimler

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