Dendritic cell (DC) modification to enhance antigen presentation is a valuable strategy in cancer immune therapy. Other than focusing on regulating interactions between DC and antigens, we intend to promote cell interactions between DC and T cell by cell surface engineering. T cell activation is greatly improved and generates higher tumor toxicity with the aid of the synthetic glycopolymer modified on the DC surface, although the glycopolymer alone shows no effect. The great promotion of DC–T cell attraction is revealed by cell image tracking in terms of both frequency and duration of contacts. Our findings provide a new method of T cell activation by these engineered “sweet DCs.” This strategy is beneficial for developing more efficient DC-based vaccines.
Cytocompatible and adhesive polyelectrolyte-based physical hydrogels with reinforced mechanical strength for small molecule delivery and detecting doses of radiotherapy.
Glycopolymer-based
drugs for immunotherapy have attracted increasing
attention because the affinity between glycans and proteins plays
an important role in immune responses. Previous studies indicate that
the polymer chain length influences the affinity. In the studies on
enhancing the immune response by glycans, it is found that both oligosaccharides
and long-chain glycopolymers work well. However, there is a lack of
systematic studies on the immune enhancement effect and the binding
ability of oligomers and polymers to immune-related proteins. In this
paper, to study the influence of the chain length, glycopolymers based
on N-acetylglucosamine with different chain lengths
were synthesized, and their interaction with immune-related proteins
and their effect on dendritic cell maturation were evaluated. It was
proved that compared with l-glycopolymers (degree of polymerization
(DP) > 20), s-glycopolymers (DP < 20) showed better binding
ability
to the dendritic cell-specific ICAM-3-grabbing nonintegrin protein
and the toll-like receptor 4 and myeloid differentiation factor 2
complex protein by quartz crystal microbalance and molecular docking
simulation. When the total sugar unit amounts are equal, s-glycopolymers
are proved to be superior in promoting dendritic cell maturation by
detecting the expression level of CD80 and CD86 on the surface of
dendritic cells. Through the combination of experimental characterization
and theoretical simulation, a deep look into the interaction between
immune-related proteins and glycopolymers with different chain lengths
is helpful to improve the understanding of the immune-related interactions
and provides a good theoretical basis for the design of new glycopolymer-based
immune drugs.
Stem
cell fate is determined by specific niches that provide multiple
physical, chemical, and biological cues. However, the hierarchy or
cascade of impact of these cues remains elusive due to their spatiotemporal
complexity. Here, anisotropic silk protein nanofiber-based hydrogels
with suitable cell adhesion capacity are developed to mimic the physical
microenvironment inside the blastocele. The hydrogels enable mouse
embryonic stem cells (mESCs) to maintain stemness in vitro in the absence of both leukemia inhibitory factor (LIF) and mouse
embryonic fibroblasts (MEFs), two critical factors in the standard
protocol for mESC maintenance. The mESCs on hydrogels can achieve
superior pluripotency, genetic stability, developmental capacity,
and germline transmission to those cultured with the standard protocol.
Such biomaterials establish an improved dynamic niche through stimulating
the secretion of autocrine factors and are sufficient to maintain
the pluripotency and propagation of ESCs. The mESCs on hydrogels are
distinct in their expression profiles and more resemble ESCs in vivo. The physical cues can thus initiate a self-sustaining
stemness-maintaining program. In addition to providing a relatively
simple and low-cost option for expansion and utility of ESCs in biological
research and therapeutic applications, this biomimetic material helps
gain more insights into the underpinnings of early mammalian embryogenesis.
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