Glycopolymers With On/Off Anchors: Confinement Effect on Regulating Dendritic Cells
Xingyu Heng,
Fangjian Shan,
He Yang
et al.
Abstract:Insufficient activation or over‐activation of T cells due to the DCs state can cause negative effects on immunotherapy, making it crucial for DCs to maintain different states in different treatments. Polysaccharides is one of the most studied substances to promote DCs maturation. However, in many methods, optimizing the spatial dimension of the interaction between polysaccharides and cells has often been overlooked. Therefore, in this paper, we propose a new strategy from the perspective of spatial dimension t… Show more
“…It is noteworthy that the concentration of copolymer grafted onto the surface for use in the DC maturation assay has been quantified at approximately 94.5 μg/mL via TG analysis. This concentration is significantly lower than previously reported levels of PMAG [15b,16] . The combination of MAG, DMC and microparticles facilitated the efficient utilization of a minimal amount of copolymer to achieve a significant impact.…”
Section: Resultsmentioning
confidence: 58%
“…Given the potential of elevated glucose levels to promote the maturation of DCs and the development of glucose‐based immune vaccines for cancer therapy, [15] we opted to employ 2‐(methacrylamido) glucopyranose (MAG) [9a,15b,16] as the primary constituent of the polymer grafted particles. Additionally, methacryloxyethyl trimethyl ammonium chloride (DMC) was chosen as the secondary monomer to enhance the interaction between polymer grafted particles and DCs [17] .…”
In the development of dendritic cell (DC) vaccines, the maturation of DCs is a critical stage. Adjuvants play a pivotal role in the maturation of DCs, with a major concern being to ensure both efficacy and safety. This study introduces an innovative approach that combines high efficacy with safety through the synthesis of micro‐adjuvants grafted with copolymers of 2‐(methacrylamido) glucopyranose (MAG) and methacryloxyethyl trimethyl ammonium chloride (DMC). The utilization of metal‐free surface‐initiated atom transfer radical polymerization enables the production of safe and recyclable adjuvants. These micrometer‐sized adjuvants surpass the optimal size range for cellular endocytosis, enabling the retrieval and reuse of them during the ex vivo maturation process, mitigating potential toxicity concerns associated with the endocytosis of non‐metabolized nanoparticles. Additionally, the adjuvants exhibit a “micro‐ligand‐mediated maturation enhancement” effect for DC maturation. This effect is influenced by the shape of the particle, as evidenced by the distinct promotion effects of rod‐like and spherical micro‐adjuvants with comparable sizes. Furthermore, the porous structure of the adjuvants enables them to function as cargo‐carrying “micro‐shuttles”, releasing antigens upon binding to DCs to facilitate efficient antigen delivery.
“…It is noteworthy that the concentration of copolymer grafted onto the surface for use in the DC maturation assay has been quantified at approximately 94.5 μg/mL via TG analysis. This concentration is significantly lower than previously reported levels of PMAG [15b,16] . The combination of MAG, DMC and microparticles facilitated the efficient utilization of a minimal amount of copolymer to achieve a significant impact.…”
Section: Resultsmentioning
confidence: 58%
“…Given the potential of elevated glucose levels to promote the maturation of DCs and the development of glucose‐based immune vaccines for cancer therapy, [15] we opted to employ 2‐(methacrylamido) glucopyranose (MAG) [9a,15b,16] as the primary constituent of the polymer grafted particles. Additionally, methacryloxyethyl trimethyl ammonium chloride (DMC) was chosen as the secondary monomer to enhance the interaction between polymer grafted particles and DCs [17] .…”
In the development of dendritic cell (DC) vaccines, the maturation of DCs is a critical stage. Adjuvants play a pivotal role in the maturation of DCs, with a major concern being to ensure both efficacy and safety. This study introduces an innovative approach that combines high efficacy with safety through the synthesis of micro‐adjuvants grafted with copolymers of 2‐(methacrylamido) glucopyranose (MAG) and methacryloxyethyl trimethyl ammonium chloride (DMC). The utilization of metal‐free surface‐initiated atom transfer radical polymerization enables the production of safe and recyclable adjuvants. These micrometer‐sized adjuvants surpass the optimal size range for cellular endocytosis, enabling the retrieval and reuse of them during the ex vivo maturation process, mitigating potential toxicity concerns associated with the endocytosis of non‐metabolized nanoparticles. Additionally, the adjuvants exhibit a “micro‐ligand‐mediated maturation enhancement” effect for DC maturation. This effect is influenced by the shape of the particle, as evidenced by the distinct promotion effects of rod‐like and spherical micro‐adjuvants with comparable sizes. Furthermore, the porous structure of the adjuvants enables them to function as cargo‐carrying “micro‐shuttles”, releasing antigens upon binding to DCs to facilitate efficient antigen delivery.
Natural killer (NK) cells, serve as the frontline defense of the immune system, and are capable of surveilling and eliminating tumor cells. Their significance in tumor immunotherapy has garnered considerable attention in recent years. However, the absence of specific receptor‐ligand interactions between NK cells and tumor cells hampers their selectivity, thereby limiting the therapeutic effectiveness of NK cell‐based tumor immunotherapy. Herein, we construct polymannose‐engineered NK (pM‐NK) cells via metabolic glycoengineering and copper‐free click chemistry. Polymannose containing dibenzocyclooctyne terminal groups (pM‐DBCO) was synthesized and covalently modified on the surface of azido‐labeled NK cells. Compared to the untreated NK cells, the interactions between pM‐NK cells and MDA‐MB‐231 cells, a breast tumor cell line with overexpression of mannose receptors, were significantly increased, and lead to significantly enhanced killing efficacy. Consequently, intravenous administration of pM‐NK cells would effectively inhibit the tumor growth and would prolong the survival of mice bearing MDA‐MB‐231 tumors. Thus, this work presents a novel strategy for tumor‐targeting NK cell‐based tumor immunotherapy.This article is protected by copyright. All rights reserved
In the development of dendritic cell (DC) vaccines, the maturation of DCs is a critical stage. Adjuvants play a pivotal role in the maturation of DCs, with a major concern being to ensure both efficacy and safety. This study introduces an innovative approach that combines high efficacy with safety through the synthesis of micro‐adjuvants grafted with copolymers of 2‐(methacrylamido) glucopyranose (MAG) and methacryloxyethyl trimethyl ammonium chloride (DMC). The utilization of metal‐free surface‐initiated atom transfer radical polymerization enables the production of safe and recyclable adjuvants. These micrometer‐sized adjuvants surpass the optimal size range for cellular endocytosis, enabling the retrieval and reuse of them during the ex vivo maturation process, mitigating potential toxicity concerns associated with the endocytosis of non‐metabolized nanoparticles. Additionally, the adjuvants exhibit a “micro‐ligand‐mediated maturation enhancement” effect for DC maturation. This effect is influenced by the shape of the particle, as evidenced by the distinct promotion effects of rod‐like and spherical micro‐adjuvants with comparable sizes. Furthermore, the porous structure of the adjuvants enables them to function as cargo‐carrying “micro‐shuttles”, releasing antigens upon binding to DCs to facilitate efficient antigen delivery.
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