<i>Toxoplasma gondii</i>-derived nanocarriers: leveraging protozoan membrane biology for scalable immune modulation and therapeutic delivery.

Abstract

Cell membrane-derived nanovesicles (CMNVs) are nanoscale lipid bilayer structures obtained from cellular membranes that serve as biomimetic drug delivery platforms, offering immune evasion, targeting, and surface functionalization capabilities. While most CMNVs originate from mammalian cells, <i>Toxoplasma gondii</i> (<i>T. gondii</i>), a genetically tractable protozoan with a structurally distinct membrane, offers a high-yield and underexplored source for producing <i>T. gondii</i>-derived CMNVs (<i>Tg</i>CMNVs). These vesicles are obtained from the parasite's plasma membrane and inner membrane complex and retain unique features including abundant GPI-anchored SRS proteins, phosphatidylthreonine-rich lipids, and an editable genome, enabling versatile engineering via genetic and chemical strategies. We review methods for <i>Tg</i>CMNV fabrication, purification, and functionalization, and evaluate their potential in immunomodulation, attenuation of tissue injury, cancer immunotherapy, and self-adjuvanting vaccine design. By combining intrinsic immune engagement with programmable surface architecture, <i>Tg</i>CMNVs could serve as a complementary and adaptable platform alongside established CMNV systems. Finally, we discuss key translational considerations, including scalable production, immunogenicity control, regulatory compliance, and stability testing, which will be essential for assessing the feasibility of <i>Tg</i>CMNVs in clinical applications.