Figure 5 |. Targeting circulating and tissue-resident immune cells.

a | “Backpacking” cells by attaching drug-releasing materials to cells ex vivo prior to adoptive transfer. IL-15 SA, interleukin-15 super agonist; PLGA, poly(lactide-co-glycolide); IFN, interferon. b | Nanoparticles (NPs) functionalized with targeting moieties can bind to circulating immune cells in the blood, which then traffic into different tissues sites with the drug carrier. cRGD, cyclic arginine-glycine-aspartic acid. c | T cell-targeted NPs deliver nucleic acid payloads (DNA or RNA) to circulating lymphocytes, resulting in the expression of chimeric antigen receptors (CARs) and other immunomodulatory gene payloads in situ. d | Albumin is used as a chaperone to transport vaccines across the epithelial barrier in the nasal and respiratory pathways through the neonatal fragment crystallisable (FcRn) receptor. NPs functionalized with hyaluronic acid are phagocytosed by macrophages and other myeloid cells at sites of intestinal inflammation in the gut. e | Systemically-injected NPs passively accumulate in tumours through the enhanced permeation and retention (EPR) effect, or functionalized NPs actively target cells such as programmed death-1 (PD-1+) lymphocytes. Alternatively, biomaterials can be directly injected into tumours to locally present or release immunostimulatory agents in the tumour microenvironment, or promote gene delivery to tumour cells for localized expression of immunomodulatory factors. f | NPs can be modified with targeting moieties or opsonization-triggering components to bind to the endothelial cells of HEVs of the inflamed draining lymph nodes or target different innate immune cells that home to sites of inflammation. cRGD, cyclic arginine-glycine-aspartic acid; HDL, high-density lipoprotein; HEV, high endothelial venules; PNAd, Peripheral lymph node addressin.