The assembly–disassembly of hyaluronic acid (HA) with a bovine serum albumin-conjugated gold nanoparticle (BSA-AuNP) was demonstrated using a gas-phase electrophoresis approach, electrospray-differential mobility analysis (ES-DMA). Physical sizes, number and mass concentrations, and degrees of aggregation of HA, BSA, and AuNP were successfully quantified using ES-DMA hyphenated with inductively coupled plasma mass spectrometry. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy was employed complementarily for an orthogonal characterization of the assembly of HA with BSA-AuNP and the subsequent HA detachment. The results show that the surface packing density of HA on BSA-AuNP was proportional to the concentration of HA (C_HA) when C_HA ≤ 5 × 10^–3 μmol/L, and the equilibrium binding constant of HA on BSA-AuNP was identified as ≈ 4 × 10⁵ L/mol at pH 3. The pH-sensitive and enzyme-induced detachments of HA from BSA-AuNP were both successfully characterized using ES-DMA and ATR-FTIR. In the absence of enzymatic catalysis, the rate constant of HA detachment (k) was shown to increase by at least 3.7 times on adjusting the environmental acidity from pH 3 to pH 7. A significant enzyme-induced HA detachment was identified at pH 7, showing a remarkable increase of k by at least two times in the presence of an enzyme. This work provides a proof of concept for assembly of HA-based hybrid colloidal nanomaterials through the tuning of surface chemistry in the aqueous phase with the ability of in situ quantitative characterization, which has shown promise for the development of a variety of HA-derivative biomedical applications (e.g., drug delivery).

中文翻译：

---

蛋白质缀合的金纳米粒子上透明质酸的组装和分离

透明质酸（HA）与牛血清白蛋白缀合的金纳米粒子（BSA-AuNP）的组装和拆卸已使用气相电泳方法，电喷雾微分迁移率分析（ES-DMA）进行了证明。使用电感耦合等离子体质谱联用的ES-DMA成功定量了HA，BSA和AuNP的物理尺寸，数量和质量浓度以及聚集度。衰减全反射傅里叶变换红外（ATR-FTIR）光谱被互补地用于HA与BSA-AuNP的组装以及随后的HA分离的正交表征。结果表明，HA对BSA-的AuNP表面填充密度为正比于HA（的浓度Ç _HA）时Ç _HA≤5×10 ^-3微摩尔/ L，并在BSA-HA的AuNP的平衡结合常数被确定为≈4×10 ⁵从BSA- HA的pH敏感和酶诱导的分队L /摩尔在pH为3。 AuNP均使用ES-DMA和ATR-FTIR成功表征。在没有酶催化的情况下，在将环境酸度从pH 3调节到pH 7时，HA脱离速率常数（k）至少增加了3.7倍。在pH 7时，酶诱导的HA脱离明显。显示k显着增加在酶的存在下至少两次。这项工作通过在水相中进行表面化学调节并具有原位定量表征的能力，为基于HA的混合胶体纳米材料的组装提供了概念验证，这为开发多种HA衍生物生物医学提供了希望应用（例如药物输送）。