Bimodal Targeting of Human Leukocytes by Fc- and CpG-Decorated Polymersomes to Tune Immune Induction

Abstract

The use of well-defined nanovesicles composed of amphiphilic block copolymers (polymersomes) for delivery of adjuvants and antigens is a promising strategy for vaccine development. However, the potency of nanoparticle vaccines depends on efficient interaction with and activation of cells involved in antigen presentation, which can be achieved by targeting cellular receptors. Here, we showed that the Fc fragment display on the polymersome surface resulted in markedly improved interactions with granulocytes, monocytes, and NK cells, while for “naked” polymersomes, virtually no binding to leukocytes was observed. Moreover, CpG-decorated polymersomes were found to also interact with T and/or B cells. Interestingly, whole blood stimulations with Fc fragment and CpG-decorated polymersomes induced interleukin (IL)-6, IL-8, and TNF-α production, while naked polymersomes did not induce any cytokine production. In conclusion, specific immune induction by polymersomes can be controlled using bimodal targeting of different immune receptors, which is an essential feature for targeted vaccine delivery.

Current Perspectives on Synthetic Compartments for Biomedical Applications

“…The external surfaces of compartments can be functionalized to attach different molecules with the aims of increasing their stability by cross-linking [ 97 ], attaching them on solid support to generate surfaces with nano/micro texture [ 98 ], or targeting specific biolocations (e.g., tumors [ 99 , 100 ] or specific organs [ 59 , 69 , 101 , 102 ]).…”

Ex Vivo Surface Decoration of Phenylboronic Acid onto Natural Killer Cells for Sialic Acid-Mediated Versatile Cancer Cell Targeting

“…Moreover, genetically modified CAR-NK cells are considered less risky than CAR-T cells, owing to highly dysfunctional and selectively killing tumor cells. 9,10 Combined with specific receptor engagers, the CAR-based engineering approach is powerful in evoking NK cell activity toward cancer cells. However, bulk production of CAR-based cells is a complicated and time-consuming process with high cost.…”

“…Natural killer (NK) is explored as an alternative therapeutic to T-cell-based approaches. Moreover, genetically modified CAR-NK cells are considered less risky than CAR-T cells, owing to highly dysfunctional and selectively killing tumor cells. , Combined with specific receptor engagers, the CAR-based engineering approach is powerful in evoking NK cell activity toward cancer cells. However, bulk production of CAR-based cells is a complicated and time-consuming process with high cost. , To overcome the limitation of genetic modification, there is an urgent need to develop alternative surface engineering techniques for NK cells.…”

Exploring the membrane fluidity of phenyl boronic acid functionalized polymersomes using the FRAP technique and their application in the pH-sensitive release of curcumin

“…[1][2][3] Polymersome-based therapeutic drug-delivery strategies have shown remarkable potential in cancer therapy due to their physical and chemical robustness. 4,5 They are spherical nanostructures that are chemically more versatile and stable than lipid-based vesicles, as well as easily functionalizable. 6 Their drug encapsulation and release capabilities can be easily tuned by functionalization, and by varying the block copolymers, which are typically biodegradable and stimuli-responsive.…”