精准纳米气体治疗研究进展

doi:10.15541/jim20170529

摘要/Abstract

摘要：

精准纳米气体治疗具有低毒高效等特性, 作为一种新兴的疾病治疗手段受到越来越多的关注。研究表明, 纳米气体治疗不仅能在特定疾病部位选择性杀死癌细胞, 还能保护正常细胞。本文总结了国际最新研究成果, 对精准纳米气体治疗的最新研究进展进行了总结归纳和展望。首先, 阐述了纳米气体治疗的治疗作用和特点; 然后, 总结了实现精准纳米气体治疗的主要途径, 包括靶向气体传输、可控气体释放、医学成像引导和监控气体治疗、基于治疗性气体的多模式联合治疗等; 最后, 对纳米气体治疗存在的问题和发展前景做出了总结和展望。

关键词: 气体治疗, 纳米药物, 可控释放, 药物传输, 介孔二氧化硅, 石墨烯, 综述

Abstract:

The precision nanomedicine-mediated gas therapy as an emerging and promising therapy strategy has received increasing attention, due to its low toxicity and high efficacy. Recent studies show that the nanomedicine-mediated gas therapy can not only kill cancer cells in specific diseased sites, but also protect normal cells. This review summarizes and reviews the most recent progress of the nanomedicine-mediated gas therapy. We introduce the therapeutic effects and characteristics of the nanomedicine-mediated gas therapy firstly, and then review several main routes to realize the precision nanomedicine-mediated gas therapy, including targeted gas delivery, controlled gas release, biomedical imaging guidance-monitoring of gas therapy, multi-model combined therapy based on therapeutic gases, and so on, and finally summarize the present existing issues and the prospects of further development in the gas therapy field.

Key words: gas therapy, nanomedicine, controlled release, drug delivery, mesoporous silica, graphene, review

中图分类号:

TB381

何前军, 陈丹阳, 范明俭. 精准纳米气体治疗研究进展[J]. 无机材料学报, 2018, 33(8): 811-824.

HE Qian-Jun, CHEN Dan-Yang, FAN Ming-Jian. Progress of Precision Nanomedicine-mediated Gas Therapy[J]. Journal of Inorganic Materials, 2018, 33(8): 811-824.

图/表 11

图1 (A)具有“笼状”结构MnCO-GON纳米药物的NIR光响应性释放CO气体的原理示意图, (B)纳米药物可控释放CO的NIR光响应性和(C)纳米药物可控释放CO的NIR光可控性[27]

Fig. 1 (A) NIR-responsive CO release mechanism of the MnCO-GON nanomedicine with a caged structure, (B) NIR responsive for CO release profiles of MnCO-GON, and (C) NIR-controllability of MnCO-GON for CO release[27] GON: Graphene Oxide Nanosheet

图2 (A)具有“三明治”结构的GON-BNN6纳米药物的π?π共轭自组装, 及其NIR光响应性释放NO气体的原理示意图, (B)纳米药物的AFM形貌表征和(C)纳米药物的NIR可控释放NO行为[28]

Fig. 2 (A) The sandwich structure of GO-BNN6 self-assembled by GO nanosheets and BNN6 molecules through the π-π stacking, and the mechanism of NIR-responsive NO release; (B) AFM data of GO-BNN6 and (C) NIR-controlled NO release profiles of the GO-BNN6 nanomedicine[28] BNN: bis-N-nitroso

图3 (A)不溶性金属配位型罗森黑盐Me-RBS的配位络合-沉淀法示意图; (B)Me-RBS的NIR光响应性释放NO气体的原理示意图; (C)Me-RBS的紫外吸收行为比较和(D)NIR光控释放NO行为比较[38]

Fig. 3 (A) Schematic illustration of the coordination-precipitation process of insoluble Me-RBS, (B) the NIR-responsive NO release mechanism of Me-RBS, (C) comparison of UV absorption behaviors of Me-RBS and (D) comparison of NO release behaviors of Me-RBS[38] RBS: Rosen Black Salt

图4 (A)具有“铃铛”结构的BNN6-SPION@hMSN纳米药物的超声响应释放NO气体的原理示意图, (B)纳米药物的TEM照片, (C)纳米药物的超声可控释放NO行为和(D)超声诱导纳米药物细胞毒性行为[41]

Fig. 4 (A) The mechanism of ultrasound-responsive NO release from the rattle-structured BNN6-SPION@hMSN nanomedicine, (B) TEM image of the nanomedicine, (C) ultrasound-responsive NO release behavior of the nanomedicine and (D) ultrasound-induced cytotoxicity of the nanomedicine[41] BNN: bis-N-nitroso; SPION: Superparamagnetic Iron Oxide-encapsulated; hMSN: hollow Mesoporous Silica Nanoparticles

图5 (A)具有“核壳”结构的PEG-USMSs-SNO纳米药物的X射线响应性释放NO气体的原理示意图, (B)纳米药物的TEM照片和元素分布图, (C)纳米药物在体外的X射线可控释放NO行为和(D)纳米药物在斑马鱼体内的X射线可控释放NO行为[42]

Fig. 5 (A) The mechanism of X-ray responsive NO release from the PEG-USMSs-SNO nanomedicine with the core-shell structure, (B) TEM images and elementary mapping of the nanomedicine, (C) X-ray controlled NO release behavior of the nanomedicine in vitro, and (D) X-ray controlled NO release behavior of the nanomedicine on zebrafish[42] USMSs: Upconversion nano-theranostic system; SNO: S-nitrosothiol.

图6 (A)基于空心介孔二氧化硅纳米载体和羰基锰前药的MnCO@hMSN纳米药物的双氧水响应性释放CO气体的原理示意图, (B)纳米药物的TEM照片和元素分布图, (C)纳米药物在体外的双氧水可控释放CO行为, (D)各种细胞内的双氧水水平比较和(E)纳米药物对各种细胞的细胞毒性研究[43]

Fig. 6 (A) The H2O2-triggered CO release mechanism of the MnCO@hMSN nanomedicine constructed by hMSN and manganese carbonyl prodrug, (B) TEM image and elementary mapping of the nanomedicine, (C) H2O2-triggered CO release behavior of the nanomedicine in vitro, (D) comparison of H2O2 levels in various cells and (E) comparison of cytotoxicity against various cells[43]hMSN: hollow Mesoporous Silica Nanoparticles

图7 (A)基于空心介孔二氧化硅纳米载体和葡萄糖氧化酶/L-精氨酸前药的Arg@hMON-GOx纳米药物的构建及其葡萄糖响应性释放NO气体的原理示意图, (B)葡萄糖浓度对双氧水浓度、pH和NO浓度的影响和(C)纳米药物对荷瘤鼠的治疗作用[44]

Fig. 7 (A) Construction and SEM image of the Arg@hMON-GOx nanomedicine based on the hMON carrier and the Arginie/GOx prodrugs, and the mechanism of glucose-responsive release of NO, (B) effects of glucose concentration on hydrogen peroxide concentration, pH and NO concentration, and (C) in vivo outcome of gas therapy by nanomedicine[44]hMON: hollow Mesoporous Organosilica Nanoparticle

图8 (A)通过介孔二氧化硅纳米载体包裹NO气体前药并涂覆磷酸钙响应层构建的新型纳米药物MSN-CaP-NO及其控释原理示意图, (B)纳米药物的酸响应NO释放行为和(C)纳米药物的光控NO释放行为[32]

Fig. 8 (A) The construction of the MSN-CaP-NO nanomedicine and its controlled NO release mechanism, (B) acid-responsive NO release behavior of the nanomedicine, and (C) light-controlled NO release profile of the nanomedicine[32]MSN: Mesoporous Silica Nanoparticles

图9 (A)具有“铃铛”结构的BNN6-SPION@hMSN纳米药物的MRI成像引导超声可控NO气体释放的原理示意图, 和(B)纳米药物的肿瘤靶向行为和MRI成像照片[41]

Fig. 9 (A) The MRI-guided ultrasound-triggered NO release mechanism of BNN6-SPION@hMSN nanomedicine, and (B) tumor-targeting property and the corresponding MRI profile[41]BNN: bis-N-nitroso; SPION: Superparamagnetic Iron Oxide-encapsulated; hMSN: hollow Mesoporous Silica Nanoparticles

图10 (A)由二氧化钛纳米粒包裹NO前药构建的纳米药物RuNO@TiO2NPs及其光控ROS和NO共释放原理示意图, (B)纳米药物的光控NO释放行为和(C)纳米药物的细胞毒性研究[48]

Fig. 10 (A) The construction of the RuNO@TiO2NPs nanomedicine and its light-controlled ROS/NO co-release mechanism, (B) behavior of light-responsive release of NO and (C) cytotoxicity profile of the nanmedicine[48]

图11 (A)mPEG-PLGA载体共担载化疗药物DOX和气体前药BNN6构建的纳米药物的光控多药共释原理示意图, (B)纳米药物的光控释放NO行为和(C)纳米药物的细胞毒性研究[31]

Fig. 11 (A) The mechanism of light-controlled multidrug co-release from the mPEG-BNN6-DOX nanomedicine, (B) behavior of UV-controlled NO release of the nanomedicine, and (C) cytotobxicity profile of the nanomedicine[31]BNN: bis-N-nitroso; DOX: Doxorubicin

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