Bioconjugation of Active Ingredients to Plant Viral Nanoparticles Is Enhanced by Preincubation with a Pluronic F127 Polymer Scaffold
Bioconjugation of Active Ingredients to Plant Viral Nanoparticles Is Enhanced by Preincubation with a Pluronic F127 Polymer Scaffold
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DOI：
10.1021/acsami.1c13183
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发表时间：
2021-12-10
影响因子：
9.5
通讯作者：
Steinmetz, Nicole F.
中科院分区：
文献类型：
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作者：
Shin, Matthew D.;Hochberg, Justin D.;Steinmetz, Nicole F.
蛋白质类纳米颗粒可用于运送大量有效成分，这在医药和农业中具有优势。然而，疏水配体与亲水性纳米载体如植物病毒纳米粒(VNPs)的偶联可通过降低总溶解度而导致聚集。考虑到亲水性纳米载体平台在靶向传递和多价配体展示方面的优势，加上疏水药物、造影剂和多肽的多功能性，这是一个必须解决的问题，以充分发挥其潜力。在这里，我们报告了两种使用Pluronic F127聚合物支架来防止结合的植物VNP聚集的预孵化策略：植物VNP聚合物预涂层(COAT)和活性成分配方与植物VNP聚合物预涂层(FORMCOAT)相结合。通过测试它们与N-羟基琥珀酰亚胺酯-胺偶联、马来酰亚胺-硫醇偶联和铜(I)催化叠氮-炔环加成(点击化学)三种生物偶联化学的兼容性，强调了这些修饰偶联策略的广泛应用。Coat和FORMCOAT策略促进了有效的生物结合，并防止了传统生物结合方法中的聚集，从而提高了植物VNP结合物在医药和农业中的稳定性、均质性和翻译潜力。
Proteinaceous nanoparticles can be used to deliver large payloads of active ingredients, which is advantageous in medicine and agriculture. However, the conjugation of hydrophobic ligands to hydrophilic nanocarriers such as plant viral nanoparticles (plant VNPs) can result in aggregation by reducing overall solubility. Given the benefits of hydrophilic nanocarrier platforms for targeted delivery and multivalent ligand display, coupled with the versatility of hydrophobic drugs, contrast agents, and peptides, this is an issue that must be addressed to realize their full potential. Here, we report two preincubation strategies that use a Pluronic F127 polymer scaffold to prevent the aggregation of conjugated plant VNPs: a plant VNP-polymer precoat (COAT) and an active ingredient formulation combined with a plant VNP-polymer precoat (FORMCOAT). The broad applications of these modified conjugation strategies were highlighted by testing their compatibility with three types of bioconjugation chemistry: N-hydroxysuccinimide ester-amine coupling, maleimide-thiol coupling, and copper(I)-catalyzed azide-alkyne cycloaddition (click chemistry). The COAT and FORMCOAT strategies promoted efficient bioconjugation and prevented the aggregation that accompanies conventional bioconjugation methods, thus improving the stability, homogeneity, and translational potential of plant VNP conjugates in medicine and agriculture.