Cellular Response to RGD Peptide Configuration on Gold Nanoparticles: A Surface Chemistry Investigation

Biosystems are exceptional mechanisms for recognizing minute molecular differences in their processes, a principle upon which modern medicine is primarily built. Nanomaterials (NMs), unlike molecules, lack a definite shape and reactivity. Their surface chemical properties serve as the primary element of their behavior in biological environments. Therefore, it is essential to understand how molecular modifications on the surface of NMs influence their functions in biosystems to optimize their use in medical and biomedical applications. Gold nanoparticles (AuNPs) with well-defined surfaces are ideal for systematic surface chemistry studies due to their inertness and low toxicity. In this study, we examined the impact of molecular orientation differences in a peptide with a CRGD sequence and its reverse sequence, DGRC, on the cellular response of A549 (human Caucasian lung carcinoma) and BEAS-2b (human bronchial epithelial cell) cell lines. One end of the peptides contains a cysteine residue to ensure binding to 13 nm AuNP surfaces from that end. When the peptides are conjugated, two distinct surface chemistries are generated: in one case, a surface with one -NH₂ and one -COOH group creates a neutral charge, while in the other, a surface with two -COOH groups generates a negative charge since the peptides are in the reverse amino acid sequences. We observed that the AuNP-CRGD-NH₂ conjugate exhibited higher uptake and caused severe cytotoxicity by inducing cell cycle arrest at the G0/G1 phase in A549 cells, whereas no significant harm was detected in BEAS-2b cells compared to the AuNP-CRGD-COOH conjugate. These results strongly suggest that the cellular response to NMs can be effectively modulated through surface chemistry. The AuNP-CRGD-NH₂ conjugate should be further evaluated for its potential therapeutic effects against lung cancer.