Hybrid transferosomes as multifunctional nanocarriers for enhanced targeted therapy and theranostic drug delivery in complex diseases

Transferosomes (TFE) are a new generation of highly deformable nanovesicular carriers designed to overcome the limitations of conventional drug delivery systems. Composed primarily of phospholipids and edge activators, TFEs exhibit high membrane flexibility, self-adjusting deformability, and good biocompatibility, thereby facilitating the non-invasive translocation of pharmaceuticals through different biological barriers, such as the stratum corneum, mucosal epithelia, and even the blood-brain barrier. Their inherent ability to increase drug permeation, deposition, and site-specific delivery makes them particularly well-positioned to enhance the pharmacokinetic and pharmacodynamic profiles of various therapeutic payloads. This review provides a comprehensive overview of traditional and hybrid TFE systems, highlighting innovations such as targeted, stimuli-responsive, and multifunctional designs that address current challenges in drug delivery. Recent developments in TFE design have enabled the development of hybrid and multifunctional systems through surface functionalization with targeting ligands, stealth polymers such as PEGylation, and stimuli-responsive moieties, allowing for controlled, stimuli-triggered, and localised drug release. These advanced modifications have positioned TFEs at the forefront of nanomedicine, demonstrating promising preclinical efficacy in cancer therapy, neurodegenerative diseases, autoimmune diseases, and infectious diseases. The multi-functionality of TFEs enables the co-delivery of therapeutic and diagnostic agents, promoting the development of theranostic nanocarriers for targeted treatment and tailored treatment strategies. TFEs emerge as a transformative nanocarrier platform, combining flexibility, stability, and multifunctionality to advance precision, targeted, and efficient drug delivery in modern medicine.