Synthesis and characterisation of ligand conjugated water soluble nano onion for intranasal drug delivery to the brain

Abstract

quotEffective delivery of anticancer drugs to specific tissues remains a major challenge in cancer therapy. Nanobiotechnology offers new opportunities through nanoscale carriers capable of targeted delivery and controlled drug release. In this work, carbon nano-onions (CNOs) were synthesized, functionalized with folic acid (FA), and loaded with carmustine (BCNU) to create a targeted nanocarrier (f-CNO-BCNU). FA was used due to its high affinity for folate receptors, which are overexpressed in many cancer cells, enabling selective recognition and uptake. TEM and DLS confirmed the size and morphology of the functionalized CNOs, and their intrinsic autofluorescence supported potential diagnostic use. newline newlineMolecular studies showed that FA-conjugated CNOs bind rapidly and non-covalently to folate receptors and are efficiently internalized. Once inside the cell, f-CNO-BCNU accumulated in the endosomal compartment and released BCNU more rapidly at acidic pH, consistent with tumor microenvironments. Biological assays demonstrated reduced cancer cell viability, decreased mitochondrial membrane potential, increased ROS generation, and apoptosis induction, while plain CNOs and f-CNOs remained biocompatible. Thus, the formulation selectively delivered BCNU to cancer cells without harming healthy cells. newline newlineComputational modeling revealed strong binding of folic acid and folinic acid (FUA) to receptor active sites through hydrophobic, electrostatic, and hydrogen-bonding interactions, supporting receptor-mediated endocytosis observed experimentally. Overall, f-CNO-BCNU represents a promising targeted chemotherapeutic platform. newline newlineFuture studies should explore transferrin-conjugated CNOs, additional anticancer drugs, and direct intranasal CNO-based delivery. A nano-formulation under 300 nm may enable nose-to-brain transport, bypassing the blood brain barrier, improving drug bioavailability, and reducing systemic toxicity for brain tumor treatment. newlinequot newline newline