Title : Development of DES-modified lignin nanoparticle and nanodiamond-based smart nano-drug delivery platforms for the treatment of Glioblastoma
Abstract:
Glioblastoma (GBM) is an aggressive and highly invasive brain tumor characterized by poor prognosis and limited therapeutic success due to the presence of the blood–brain barrier (BBB) and intrinsic treatment resistance. Conventional treatment strategies, including surgery, radiotherapy, and chemotherapy, remain insufficient in achieving long-term disease treatment. In particular, the limited BBB permeability and rapid systemic degradation of chemotherapeutic agents such as temozolomide (TMZ) significantly reduce treatment efficacy. Therefore, development of advanced, targeted, and biocompatible drug delivery systems is critically needed.
In this study, we report the development of a novel, environmentally sustainable nano-drug delivery platform based on deep eutectic solvent (DES)-modified nanodiamonds (ND) and lignin-derived nanoparticles (LNPs). Both nanocarrier systems were synthesized and functionalized using DES under green chemistry principles, enabling controlled surface modification while preserving structural integrity. Recycled lignin was utilized as a renewable carbon source for nanoparticle synthesis, contributing to the sustainability and cost-effectiveness of the platform. Physicochemical characterization studies (zeta potential, DLS, FT-IR, XRD, SEM) demonstrated that DES modification significantly improved the colloidal stability of the nanoparticles, reduced their aggregation tendency, and enhanced experimental reproducibility. In addition, the introduction of new surface functional groups strengthened potential biological interactions while preserving the fundamental structural integrity of the nanomaterials. The resulting systems exhibited optimized hydrodynamic sizes (130–180 nm) and low polydispersity indices, indicating their suitability for efficient cellular uptake and potential BBB penetration.
Building on these favorable physicochemical properties, the drug loading capacity of the nanocarriers was subsequently evaluated using temozolomide as a model chemotherapeutic agent. Temozolomide was loaded onto both nanocarrier systems via physical adsorption, and drug loading efficiency was quantified using UV–Vis spectroscopy. In vitro release studies demonstrated controlled and pH-responsive drug release behavior, with enhanced release under tumor-mimicking acidic conditions (pH 6.4) compared to physiological conditions (pH 7.4). These findings indicate that the developed systems exhibit pH-responsive drug release behavior, with enhanced release under mildly acidic conditions mimicking the tumor microenvironment. To further evaluate their suitability for biomedical applications, the biocompatibility and cytotoxicity profiles of the nanocarriers were investigated. Biocompatibility and cytotoxicity were assessed using MTT assays on HEK-293T cells. The results indicated low toxicity and high biocompatibility for both ND and LNP systems, with some concentrations promoting cell viability. These findings support their potential safety for biomedical applications.
