Reproducible and controlled peptide functionalization of polymeric nanoparticles
Reproducible and controlled peptide functionalization of polymeric nanoparticles
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聚合物纳米颗粒的可再现和受控的肽官能化
DOI：
10.3389/fbiom.2022.1003172
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发表时间：
2022-10
期刊：
影响因子：
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通讯作者：
Indika Chandrasiri;Yuxuan Liu;Emmanuela Adjei-Sowah;Baixue Xiao;D. Benoit
中科院分区：
文献类型：
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作者：
Indika Chandrasiri;Yuxuan Liu;Emmanuela Adjei-Sowah;Baixue Xiao;D. Benoit
含有多个胺和羧酸盐的聚合物纳米颗粒在药物传递研究中被频繁地使用。为了实现高效的药物释放平台，这些多功能生物材料之间的可重复性和可控的偶联是必要的。然而，多个官能团增加了分子内/分子间在连接过程中发生意外反应的风险。本文研究了多胺功能化多肽、多羧酸盐功能化聚合物和含酸酐聚合物[聚(苯乙烯-α-马来酸酐)-b-聚苯乙烯]在不同的共轭策略(碳二亚胺化学、亲核加成消除开环)下的共轭途径和可能发生的不良反应。多胺多肽导致聚合物之间的广泛交联性，而与共轭化学无关。结果还表明，常规的多肽定量方法(即邻苯二甲醛测定法、比辛酸测定法)是不可靠的。凝胶渗透色谱(GPC)为分子间交联提供了更准确的定性和定量证据。交联密度与多功能多肽和碳二亚胺偶联剂的进料比高相关。选择性保护的多肽(Lys-Allc)没有交联性，并产生了分散性和相对分子质量可控的多肽-聚合物偶联物。此外，酸酐开环(ARO)亲核加成消除被成功地引入作为一种简单而健壮的环酸酐聚合物的多肽共轭方法。图形摘要
Polymeric nanoparticles containing multiple amines and carboxylates have been frequently used in drug delivery research. Reproducible and controlled conjugation among these multifunctional biomaterials is necessary to achieve efficient drug delivery platforms. However, multiple functional groups increase the risk of unintended intramolecular/intermolecular reactions during conjugation. Herein, conjugation approaches and possible undesired reactions between multi-amine functionalized peptides, multi-carboxylate functionalized polymers, and anhydride-containing polymers [Poly(styrene-alt-maleic anhydride)-b-poly(styrene)] were investigated under different conjugation strategies (carbodiimide chemistry, anhydride ring-opening via nucleophilic addition elimination). Muti-amine peptides led to extensive crosslinking between polymers regardless of the conjugation chemistry. Results also indicate that conventional peptide quantification methods (i.e., o-phthalaldehyde assay, bicinchoninic acid assay) are unreliable. Gel permeation chromatography (GPC) provided more accurate qualitative and quantitative evidence for intermolecular crosslinking. Crosslinking densities were correlated with higher feed ratios of multifunctional peptides and carbodiimide coupling reagents. Selectively protected peptides (Lys-Alloc) exhibited no crosslinking and yielded peptide-polymer conjugates with controlled dispersity and molecular weight. Furthermore, anhydride ring-opening (ARO) nucleophilic addition elimination was successfully introduced as a facile yet robust peptide conjugation approach for cyclic anhydride-containing polymers. Graphical Abstract