Design and performance of hollow mesoporous SiO2-based nanodrug carrier materials with controllable particle size
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摘要: 本文分别以聚丙烯酸(PAA)、正硅酸乙酯(TEOS)、硅烷偶联剂Si-69，异硫氰酸荧光素(FITC)为软模板，主要原料为荧光剂，利用自模板法制备具有荧光标记的中空介孔SiO2纳米载体(HMSNs-69-FITC)。通过FTIR、DLS、BET、Raman和TEM对纳米载体的结构、粒径进行测定，用紫外分光光度计和TEM对其还原敏感性能进行表征，用溶剂挥发法负载索拉非尼(SOR)，并计算其负载效率。研究结果表明，调控PAA的量可以实现HMSNs在25~380 nm范围内粒径可控，其中，0.024 g/mL PAA、平均粒径100 nm的HMSNs稳定性能优良，HMSNS-69-FITC对SOR的负载效率为280.0 μg/mg，在含有0.0083 g/mL二硫苏糖醇(DTT)的PBS溶液中，48 h累计释放率约为82.4%；而无DTT时，48 h累计释放率约为25.1%，该载体具有二硫键还原敏感性。此研究工作有助于推动粒径可控的、还原敏感型SiO2纳米载体领域的研究。Abstract: In this study, polyacrylic acid (PAA), ethyl orthosilicate (TEOS), silane coupling agent Si-69, fluorescein isothiocyanate (FITC) were used as soft templates, the main raw materials, fluorescent agents, and fluorescent agents were used to prepare hollow mesoporous SiO2 nanocarriers (HMSNs-69-FITC) with fluorescent labeling by self-template method. The structure and particle size of nanocarriers were determined by FTIR, DLS, BET, Raman and TEM, their reduction-sensitive properties were characterized by ultraviolet spectrophotometer and TEM, and sorafenib (SOR) was loaded with solvent volatilization, and calculate its load efficiency. The results show that the amount of regulating PAA can achieve controllable particle size of HMSNs in the range of 25-380 nm, among which, HMSNs with 0.024 g/mL PAA and an average particle size of 100 nm have excellent stability performance, HMSNs-69-FITC has a loading efficiency of 280.0 μg/mg for SOR, and in PBS solution containing 0.0083 g/mL dithiothreitol (DTT), the cumulative release rate of 48 h is about 82.4%. In the absence of DTT, the cumulative release rate at 48 h is about 25.1%, which has significant disulfide bond reduction sensitivity. This work helps advance research in the field of particle size controllable and reduction-sensitive SiO2 nanocarriers.
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图 1 (a) 聚丙烯酸酯铵(APA)制备流程；(b) 中空复合型SiO2纳米载体(HMSNs-69)的制备流程；(c) HMSNs-69的硫氰酸荧光素修饰(HMSNs-69-FITC)形成路线
Figure 1. (a) Preparation process of APA; (b) Preparation process of hollow mesoporous SiO2 nanocarriers (HMSNs)-69; (c) Formation route of HMSNs-69-fluorescein isothiocyanate (FITC)
图 2 不同聚丙烯酸(PAA)含量的软模板的SEM图像： 0.02 g (a1)、0.12 g (a2)、0.22 g (a3)、0.32 g (a4)、0.42 g (a5)、0.52 g (a6)；不同PAA含量制备得HMSNs的TEM图像：0.02 g (b1)、0.12 g (b2)、0.22 g (b3)、0.32 g (b4)、0.42 g (b5)、0.52 g (b6)
Figure 2. SEM images of soft template with different contents of polyacrylic acid (PAA): 0.02 g (a1), 0.12 g (a2), 0.22 g (a3), 0.32 g (a4), 0.42 g (a5), and 0.52 g (a6); TEM images of HMSNs with different contents of PAA: 0.02 g (b1), 0.12 g (b2), 0.22 g (b3), 0.32 g (b4), 0.42 g (b5), and 0.52 g (b6)
图 3 不同PAA含量制备的HMSNs的动态光散射(DLS)图： 0.02 g (a)、0.12 g (b)、0.22 g (c)、0.32 g (d)、0.42 g (e)、and 0.52 g (f)
Figure 3. Dynamic light scattering (DLS) plot of HMSNs with different PAA amounts: 0.02 g (a), 0.12 g (b), 0.22 g (c), 0.32 g (d), 0.42 g (e), and 0.52 g (f)
图 4 PAA的添加量与粒径函数关系
Figure 4. Functional relationship of between the amount of PAA and the particle size
图 5 不同正硅酸乙酯(TEOS)/硅烷偶联剂Si-69体积比制得HMSNs-69的TEM图像：1.2/1.8 ((a1)~(a4))、1.5/1.5 ((b1)~(b4))、1.8/1.2 ((c1)~(c4))、2.2/0.8 ((d1)~(d4))、2.6/0.4 ((e1)~(e4))
Figure 5. TEM images of HMSNs-69 prepared by volume ratios of different ethyl orthosilicate (TEOS)/silane coupling agent Si-69: 1.2/1.8 ((a1)-(a4)), 1.5/1.5 ((b1)-(b4)), 1.8/1.2 ((c1)-(c4)), 2.2/0.8 ((d1)-(d4)), and 2.6/0.4 ((e1)-(e4))
图 6 HMSNs-69的吸附脱附等温线(a)、脱附微分积分的孔体积-孔径对数分布曲线(b)
Figure 6. Adsorption desorption isotherms (a), logarithmic distribution curve of volume aperture of differential integral holes (b) of HMSNs-69
图 7 HMSNs-69的SEM图像(a)、EDS能谱图(C元素(b)、O元素(c)、Si元素(d)、S元素(e))和元素分布图谱(f)
Figure 7. SEM image (a), EDS spectra (C element (b), O element (c), Si element (d), S element (e)) and element distribution map (f) of HMSNs-69
图 8 (a) Si-69、HMSNs和HMSNs-69的拉曼图谱；(b) FITC、HMSNs-69和HMSNs-69-FITC的荧光色谱；(c) HMSNs、HMSNs-69和HMSNs-69-FITC的红外图谱
Figure 8. (a) Raman spectra of Si-69, HMSNs and HMSNs-69; (b) Fluorescence chromatography of FITC, HMSNs-69 and HMSNs-69-FITC; (c) Infrared spectra of HMSNs, HMSNs-69 and HMSNs-69-FITC
图 9 —S—S—和二硫苏糖醇(DTT)的氧化还原反应过程[30]、实验组和对照组的紫外吸收强度随时间的变化情况(b)、HMSNs-69-FITC降解前(c1)、降解7天(c2)、降解15天(c3)的SEM图像
Figure 9. —S—S— and dithiothreitol (DTT) redox reaction process[30](a), changes of UV absorption intensity over time in the experimental group and the control group (b), SEM images of HMSNs-69-FITC before degradation (c1), after degradation 7 days (c2), and 15 days (c3)
图 10 (a) HMSNs-69-FITC负载药物的紫外光谱；(b) HMSNs-69-FITC在48 h内药物释放情况；(c) 索拉非尼标准曲线
Figure 10. (a) UV spectra of HMSNs-69-FITC-loaded drugs; (b) Drug release of HMSNs-69-FITC within 48 h; (c) Sorafenib standard curve
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