Organization from cell to tissue derived delivery systems for immunotherapy

Abstract

Dysregulation of the immune system drives a broad spectrum of diseases, including cancers, autoimmune disorders, and neuro-immune conditions. Immunotherapy has advanced from small-molecule drugs to biomacromolecular agents and living cell therapies, yet conventional synthetic delivery platforms struggle to preserve the structural integrity, bioactivity, and long-term viability of these complex payloads in vivo. Biologically derived drug delivery systems (BDDS) have emerged as a promising class of carriers that harness natural organelles, cells, and tissues to achieve high loading capacity, inherent biocompatibility, bioresponsive targeting, and controlled release. This review systematically examines the hierarchical organization of BDDS across nanoscale, microscale, and macroscale levels and emphasizes their distinct biological advantages, engineering features, and translational potential. We detail the material sourcing, isolation techniques, drug-loading, surface modification, and genetic engineering strategies, as well as considerations for scalable manufacturing. Representative platforms are highlighted for their ability to cross biological barriers, modulate immune microenvironment, and treat cancers, autoimmune diseases, and neuroinflammation. In addition, the emerging biosynthetic alternatives including membraneless organelle condensates, artificial cells, and advanced organoids, are discussed as next-generation platforms that may overcome the limitations of natural BDDS. Finally, we outline current challenges in the heterogeneity, large-scale production, and clinical translation, while proposing future directions including the reasonable administration routes, cross-scale hierarchical integrated platform designs and emerging computational and engineering technologies to accelerate the development of BDDS-based immunotherapies.