Nanoparticle Chemistry and Functionalization Differentially Regulates Dendritic Cell-Nanoparticle Interactions and Triggers Dendritic Cell Maturation
Nanoparticle Chemistry and Functionalization Differentially Regulates Dendritic Cell-Nanoparticle Interactions and Triggers Dendritic Cell Maturation
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DOI：
10.1002/ppsc.201400148
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发表时间：
2014-12-01
影响因子：
2.7
通讯作者：
Narasimhan, Balaji
中科院分区：
文献类型：
--
作者：
Goodman, Jonathan T.;Ramirez, Julia E. Vela;Narasimhan, Balaji
可生物降解的聚酸酐纳米颗粒已被用作疫苗佐剂和递送载体。在肠胃外给药后，这些纳米颗粒的表面特征可以通过血清蛋白吸附而改变，可能影响颗粒如何与抗原呈递细胞相互作用。这些研究调查了血清蛋白的差异吸附到不同化学性质的碳水化合物官能化和非官能化聚酸酐纳米颗粒上对与树突状细胞（DC）相互作用的作用。将二甘露糖（1，2-α-连接的-D-吡喃甘露糖苷的羧甲基修饰的二糖）或乙醇酸共价连接到使用1，6-双（对羧基苯氧基）己烷（CPH）和癸二酸（SA）以及1，8-双（对羧基苯氧基）-3，6-二氧杂辛烷（CPTEG）和CPH的共聚物合成的纳米颗粒。血清蛋白吸附CPH：SA纳米颗粒增强颗粒内化，但没有增强摄取CPTEG：CPH纳米颗粒。当DC与纳米颗粒一起培养时，MHCII，CD 86和CD 206的表面表达增强，并由聚合物化学和功能化介导。DC的细胞因子分泌受到聚合物化学和功能化的差异调节。血清蛋白的吸附量和分布表明，聚合物的疏水性和功能化增强蛋白吸附。整体的聚合物化学，功能化，和血清蛋白吸附影响纳米颗粒与树突状细胞的相互作用，阐明这些参数和树突状细胞成熟之间的复杂关系，将使合理的靶向疫苗和免疫治疗的设计。
Biodegradable polyanhydride nanoparticles have been used as vaccine adjuvants and delivery vehicles. Upon parenteral administration, the surface characteristics of these nanoparticles may be modified by serum protein adsorption, likely affecting how the particles interact with antigen presenting cells. These studies investigated the role of the differential adsorption of serum proteins onto carbohydrate-functionalized and non-functionalized polyanhydride nanoparticles of different chemistries on interactions with dendritic cells (DCs). Di-mannose (a carboxymethyl-modified disaccharide of 1,2-alpha-linked-D-mannopyranoside) or glycolic acid was covalently linked to nanoparticles synthesized using copolymers of 1,6-bis(p-carboxyphenoxy) hexane (CPH) and sebacic acid (SA) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and CPH. Serum protein adsorption to CPH: SA nanoparticles enhanced particle internalization, but did not enhance uptake of CPTEG: CPH nanoparticles. When DCs were cultured with nanoparticles, the surface expression of MHC II, CD86, and CD206 was enhanced and mediated by both polymer chemistry and functionalization. Cytokine secretion by DCs was differentially modulated by both polymer chemistry and functionalization. The amount and profile of serum proteins adsorbed indicated that polymer hydrophobicity and functionalization enhanced protein adsorption. Overall polymer chemistry, functionalization, and serum protein adsorption influenced nanoparticle interactions with DCs and elucidating the complex relationships between these parameters and dendritic cell maturation will enable rational design of targeted vaccines and immunotherapies.