基于cypate光裂解的新型近红外光响应稀土上转换纳米载药系统※

doi:10.6023/A22010001

化学学报 ›› 2022, Vol. 80 ›› Issue (4): 423-427.DOI: 10.6023/A22010001 上一篇下一篇

所属专题：中国科学院青年创新促进会合辑

研究通讯

基于cypate光裂解的新型近红外光响应稀土上转换纳米载药系统^※

刘若湄^a^,^b, 冯艳辉^a^,^b, 李卓^b, 卢珊^a^,^b^,^*(), 关天用^b, 李幸俊^b, 刘䶮^b, 陈卓^b, 陈学元^a^,^b^,^*()

a 福州大学化学学院福州 350108
b 中国科学院福建物质结构研究所中国科学院功能纳米结构设计与组装重点实验室福州 350002

投稿日期:2022-01-01 发布日期:2022-04-28
通讯作者: 卢珊, 陈学元
作者简介:
^※ 庆祝中国科学院青年创新促进会十年华诞.
基金资助:
国家自然科学基金(12174392); 国家自然科学基金(22175179); 国家自然科学基金(22135008); 福建省自然科学基金(2021I0040); 福建省自然科学基金(2021L3024); 福建省自然科学基金(2021Y0067)

A Novel Near-infrared Responsive Lanthanide Upconversion Nanoplatform for Drug Delivery Based on Photocleavage of Cypate^※

Ruomei Liu^a^,^b, Yanhui Feng^a^,^b, Zhuo Li^b, Shan Lu^a^,^b(), Tianyong Guan^b, Xingjun Li^b, Yan Liu^b, Zhuo Chen^b, Xueyuan Chen^a^,^b()

a College of Chemistry, Fuzhou University, Fuzhou 350108, China
b CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China

Received:2022-01-01 Published:2022-04-28
Contact: Shan Lu, Xueyuan Chen
About author:
^※ Dedicated to the 10th anniversary of the Youth Innovation Promotion Association, CAS.
Supported by:
National Natural Science Foundation of China(12174392); National Natural Science Foundation of China(22175179); National Natural Science Foundation of China(22135008); Natural Science Foundation of Fujian Province(2021I0040); Natural Science Foundation of Fujian Province(2021L3024); Natural Science Foundation of Fujian Province(2021Y0067)

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1. Supporting Information-A22010001.pdf(778KB)

摘要/Abstract

光响应药物释放体系具有非侵入性、远程可控且时空分辨率高等特点, 在杀菌、抗癌等生物医学领域具有重要应用价值. 但目前近红外光响应的光裂解药物递送体系报道较少且光响应效率还有待提高. 本工作将稀土纳米颗粒包覆介孔二氧化硅, 逐步偶联近红外染料cypate、金刚烷胺和β-环糊精来封堵孔口, 利用cypate的自敏光氧化断键作为光响应开关, 成功构建了一种新型近红外光响应稀土上转换纳米载药系统. 该纳米载药系统负载抗生素氧氟沙星表现出极低的药物流失率和较高的808 nm光照释放效率, 并且通过控制光照时间可以满足不同的给药量需求. 体外抗菌实验结果进一步验证了该纳米载药系统的光响应药物释放性能. 此外, 该纳米载药系统在980 nm激光激发下的上转换发光较强且不影响药物释放, 可以实现纳米载药系统的药物定位和生物成像功能. 本研究为发展高效光响应载药体系提供了新的思路.

关键词: 上转换纳米颗粒, 近红外光响应, 近红外染料, 药物递送, 光裂解

Light-responsive drug delivery systems (DDS) exhibit the advantages of non-invasive, high controllability and spatio-temporal precision. However, DDS triggered by near-infrared (NIR) light are few and inefficient. In this work, we designed a novel NIR-responsive upconversion nanoplatform for drug delivery. In this nanoplatform, core-shell upconversion nanoparticle (UCNP) NaYF₄:Yb,Er@NaYF₄ was coated by mesoporous silica, and then successively coupled with NIR dye cypate, amantadine (AD) and β-cyclodextrin (β-CD) to block the pores and entrap the drugs. The cypate molecules with the feature of auto-sensitized photooxidation under 808 nm irradiation were, for the first time, employed as light-responsive moieties in DDS. The obtained nanoplatform was characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), N₂ adsorption/desorption, dynamic light scattering (DLS) and zeta potential analysis. Mechanism of photocleavage of cypate by singlet oxygen (¹O₂) was also investigated by electron spin resonance (ESR) measurement. The nanoplatform loaded with antibiotic ofloxacin (OFL) showed a low drug leakage (6.9%) in the dark condition and a rapid release (50.9%) upon 808 nm irradiation with a relatively low power density of 0.5 W•cm^-2 for 40 min. Moreover, on-demand release of OFL can be achieved by adjusting the irradiation time (0~40 min). In vitro antibacterial experiments showed that the nanoplatform had a much better antibacterial effect against Staphylococcus aureus after 808 nm irradiation as compared with the group without irradiation. These results further verified the excellent NIR-responsive performance for the designed nanoplatform. In addition, the nanoplatform exhibited strong and stable upconversion luminescence (UCL) under 980 nm excitation, which can be applied for DDS tracing and bioimaging. The cytocompatibility of the nanoplatform was evaluated by methyl thiazolyl tetrazolium (MTT) assay, showing that the nanoplatform had no cytotoxic effect on human embryonic liver cell line (LO2) and exhibited great potentials in versatile bioapplications. Our work may open up a new avenue for the exploration of multi-functional NIR-responsive DDS.

Key words: upconversion nanoparticles, near-infrared light-responsive, near-infrared dye, drug delivery, photocleavage

引用此文

刘若湄, 冯艳辉, 李卓, 卢珊, 关天用, 李幸俊, 刘䶮, 陈卓, 陈学元. 基于cypate光裂解的新型近红外光响应稀土上转换纳米载药系统^※[J]. 化学学报, 2022, 80(4): 423-427.

Ruomei Liu, Yanhui Feng, Zhuo Li, Shan Lu, Tianyong Guan, Xingjun Li, Yan Liu, Zhuo Chen, Xueyuan Chen. A Novel Near-infrared Responsive Lanthanide Upconversion Nanoplatform for Drug Delivery Based on Photocleavage of Cypate^※[J]. Acta Chimica Sinica, 2022, 80(4): 423-427.

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图/表 4

图1. 近红外光响应纳米载药系统的构建及应用示意图

Figure 1. Illustration of the fabrication of near-infrared (NIR) light responsive upconversion nanoplatform for drug delivery

图2. (A) UCNP和(B) UCNP@MS的TEM图. (C) UCNP和UCNP@MS的XRD图. (D) UCNP@MS的氮气吸附-脱附等温线和孔径分布图. (E) UCNP@MS、UCNP@MS-NH2和UCNP@MS-NH2-cypate的zeta电位. (F) UCNP@MS、UCNP@MS-cypate-AD、OFL-UCNP@MS-cypate@β-CD水溶液中的粒径分布图. (G) UCNP@MS、UCNP@MS-cypate-AD、OFL-UCNP@MS-cypate@β-CD及OFL的紫外-可见-近红外吸收光谱. (H) UCNP@MS、UCNP@MS-cypate-AD和OFL-UCNP@MS-cypate@β-CD的红外谱图

Figure 2. TEM images of (A) UCNP and (B) UCNP@MS. (C) XRD patterns of UCNP and UCNP@MS. (D) N2 adsorption/desorption isotherm and pore size distribution of UCNP@MS. (E) Zeta potentials of UCNP@MS, UCNP@MS-NH2, UCNP@MS-NH2-cypate. (F) Hydrodynamic size distributions of UCNP@MS, UCNP@MS-cypate-AD and OFL-UCNP@MS-cypate@β-CD. (G) UV-Vis-NIR absorption spectra of UCNP@MS, UCNP@MS-cypate-AD, OFL-UCNP@MS-cypate@β-CD and OFL. (H) FT-IR spectra of UCNP@MS, UCNP@MS-cypate-AD, and OFL-UCNP@MS-cypate@β-CD

图3. (A) 808 nm激发下OFL-UCNP@MS-cypate@β-CD的吸收光谱变化. (B) 不同体系中cypate光裂解效率比较. (C) cypate光裂解机理. (D) 808 nm激光照射后OFL-UCNP@MS-cypate@β-CD的顺磁波谱

Figure 3. (A) Variation of absorption spectra of OFL-UCNP@MS-cypate@β-CD under excitation at 808 nm. (B) Comparison of photocleavage efficiency of cypate in different nanoplatforms. (C) Mechanism of photocleavage of cypate by 1O2. (D) ESR spectrum of OFL-UCNP@MS-cypate@β-CD after 808 nm laser irradiation

图4. (A) 808 nm光照下从纳米载药系统逐步释放的OFL的吸收谱. (B) 不同808 nm激光照射时间下的纳米载药系统的OFL释放曲线. (C) 纳米载药体统在药物释放前后的980 nm激发上转换光谱以及发光照片. (D) 不同处理条件对金黄色葡萄球菌的抗菌效果. (E)纳米载药系统孵育金黄色葡萄球菌的CLSM图像, 从左至右分别为(i)明场像、(ii) 980 nm激光照射下的绿色上转换发光成像以及(iii)叠加图像

Figure 4. (A) Absorption spectra of OFL released from nanoplatform with time under 808 nm irradiation. (B) Release profiles of OFL from nanoplatform with different irradiation time of 808 nm. (C) Upconverson luminescence (UCL) spectra and corresponding UCL photographs of nanoplatform excited by 980 nm before and after drug release. (D) Antibacterial effect on Staphylococcus aureus (SA) with different treatments. (E) CLSM images of SA incubated with nanoplatform: (i) bright-field image, (ii) green UCL image excited by 980 nm, and (iii) the overlay image

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基于cypate光裂解的新型近红外光响应稀土上转换纳米载药系统^※

A Novel Near-infrared Responsive Lanthanide Upconversion Nanoplatform for Drug Delivery Based on Photocleavage of Cypate^※

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基于cypate光裂解的新型近红外光响应稀土上转换纳米载药系统※

A Novel Near-infrared Responsive Lanthanide Upconversion Nanoplatform for Drug Delivery Based on Photocleavage of Cypate※

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基于cypate光裂解的新型近红外光响应稀土上转换纳米载药系统^※

A Novel Near-infrared Responsive Lanthanide Upconversion Nanoplatform for Drug Delivery Based on Photocleavage of Cypate^※