Speakers - 2026

Title: PEGylated graphene oxide nanocarriers for 4’-Fluorouridine delivery: An ab initio framework for antiviral and tumor-targeted therapy

Abstract

The rapid emergence of viral pathogens such as SARS-CoV-2 underscores the urgency for efficient, adaptable antiviral drug delivery systems. 4’-Fluorouridine (4’-FlU), a nucleoside analogue with potent broad-spectrum antiviral activity, presents formulation challenges that limit its therapeutic potential. This study employs ab initio density functional theory (DFT) simulations to elucidate the physicochemical interactions governing 4’-FlU delivery via graphene oxide (GO) nanocarriers, both unmodified and polyethylene glycol (PEG) functionalized, across physiologically relevant environments (gas, aqueous, acidic, and alkaline). Adsorption energy analysis revealed that non-PEGylated GO exhibits high gas-phase binding (−103.36 kcal/mol), favoring systemic stability, while PEGylation reduces aqueous-phase binding (−33.72 kcal/mol) but improves biocompatibility and circulation time. In acidic and alkaline environments, PEGylated GO intensifies binding (−100.86 and −118.42 kcal/mol, respectively), driven by enhanced hydrogen bonding. Charge transfer dynamics demonstrated pH-dependent stability, with acidic conditions supporting prolonged retention—critical for tumor microenvironments. Reduced Density Gradient (RDG) and miscibility studies confirmed that PEGylation optimizes compatibility in acidic phases. Release kinetics indicated that PEGylation in acidic conditions enables controlled release (τ ≈ 7.26 × 10 60 ms), while aqueous PEG-GO systems achieve faster release suitable for systemic antiviral delivery. Thermodynamic analysis (ΔG < 0 across all phases) confirmed spontaneous, energetically favorable interactions, and quantum descriptors identified GO/PEG–4’-FlU as electronically stable in aqueous media (Eg = 0.63 eV). These findings establish a molecular-level framework for designing PEGylated GO nanocarriers capable of targeted drug release in acidic environments, such as tumors, while retaining adaptability for systemic antiviral therapy. The ab initio methodology employed here also provides a predictive platform for screening next-generation nanomedicine formulations prior to experimental validation.

Audience Takeaways

• Understand how PEGylation modulates drug–nanocarrier interactions under diverse physiological conditions.
• Learn the pH-responsive binding and release profiles relevant to antiviral and tumor-targeted applications.
• Gain insights into integrating quantum chemical descriptors into nanocarrier design workflows.
• Recognise the thermodynamic and kinetic parameters critical for controlled drug delivery.
• Apply in silico methodologies to accelerate nanomedicine development.