中国药学杂志

Methods	Nanoparticles	Preparation	Morphology and size	Characterization methods	Application	Reference
Biological method	Au-Ganoderma lucidum nanoparticles	Green synthesis	Spherical,oval and irregular, 1-100 nm	UV-Vis,XRD,EDX,TEM	Inhibited HT-29 colon cancer cell line	[26]
	Ag-Ganoderma lucidum nanoparticles	Green synthesis	Spherical,9-21 nm	XPS,XRD,TEM,UV-Vis,FTIR	Antioxidant and antibacterial	[27]
		Green synthesis	Spherical,11-16 nm	UV-Vis,XRD,FTIR,SEM,TEM	Antioxidant,antibacterial and inhibited the human epidermic carcinoma cancer cell line	[28]
		Green synthesis	Spherical,23-58 nm	UV-Vis,XRD,SEM,FTIR	Antioxidant,antibacterial and inhibited the breast cancer cell line-MDA-MB-231	[29]
		Green synthesis	Spherical,(133.0±0.361)nm	UV-Vis,FTIR,Zeta,SEM	Antibacterial	[30]
		Green synthesis	Spherical,200 nm	TEM,DLS,XRF	-	[31]
	ZnO-Ganoderma lucidum nan- oparticles	Green synthesis	“Petals”,50-200 nm	XRD,TEM,UV-Vis,PL	Detect Rhodamine	[32]
	Se-Ganoderma lucidum nanoparticles	Green synthesis	Spherical,<50 nm	TEM,EDS,SEM	-	[33]
	Si-Ganoderma lucidum nanoparticles	Green synthesis	200-300 nm	TEM,XRD,SAED	-	[34]
	CuO-Ganoderma lucidum nanoparticles	Green synthesis	Spherical,4-5 nm	UV-vis,TEM,FTIR,XRD,DLS	Antibacterial	[35]
Chemical method	Ganoderma lucidum polysaccharides as nanocarriers with main chains	Nanoprecipitation method	(54.76±3.72)nm	HPLC,TEM,DLS	Anticancer	[36]
		Nanoprecipitation method	60 nm	H-NMR,TEM	Drug carrier	[37]
		Nanoprecipitation method	Spherical,300 nm	FTIR,TEM,HNMR	Drug carrier	[38]
		Nanoprecipitation method	Spherical,190 nm	TEM,DLS	Drug carrier	[39]
	Ganoderma lucidum nanoemulsion	Emulsified solvent evaporation method	Spherical,50-200 nm	Zeta,TEM	-	[40]
	Nanoemulsion of Ganoderma spore oil as oil phase	Emulsified solvent evaporation method	Spherical,(141.92±3.38)nm	Cryo-SEM,Zeta	Enhance the immunity	[41]
	Nanoemulsion of Ganoderma lucidum polysaccharides in aqueous phase	Emulsification method	70.08±3.15 nm	DSC,PXRD,SEM	Drug carrier	[42]
		Emulsification method	Spherical,35-37 nm	HPLC,Zeta,DSC,PXRD,SEM	Drug carrier	[43]
		Emulsification method	Spherical,(54.23±1.02)nm	Zeta,AOR,Dt,SEM,TEM,DSC,PXRD	Anti-diabetes and anti-oxidation as a drug carrier	[44]
Physical method	Ganoderma lucidum nanoparticles	Machine crushing	500 nm	SEM	Inhibited HeLa cells	[45]

Methods	Nanoparticles	Preparation	Morphology and size	Characterization methods	Application	Reference
Biological method	Au-Ganoderma lucidum nanoparticles	Green synthesis	Spherical,oval and irregular, 1-100 nm	UV-Vis,XRD,EDX,TEM	Inhibited HT-29 colon cancer cell line	[26]
	Ag-Ganoderma lucidum nanoparticles	Green synthesis	Spherical,9-21 nm	XPS,XRD,TEM,UV-Vis,FTIR	Antioxidant and antibacterial	[27]
		Green synthesis	Spherical,11-16 nm	UV-Vis,XRD,FTIR,SEM,TEM	Antioxidant,antibacterial and inhibited the human epidermic carcinoma cancer cell line	[28]
		Green synthesis	Spherical,23-58 nm	UV-Vis,XRD,SEM,FTIR	Antioxidant,antibacterial and inhibited the breast cancer cell line-MDA-MB-231	[29]
		Green synthesis	Spherical,(133.0±0.361)nm	UV-Vis,FTIR,Zeta,SEM	Antibacterial	[30]
		Green synthesis	Spherical,200 nm	TEM,DLS,XRF	-	[31]
	ZnO-Ganoderma lucidum nan- oparticles	Green synthesis	“Petals”,50-200 nm	XRD,TEM,UV-Vis,PL	Detect Rhodamine	[32]
	Se-Ganoderma lucidum nanoparticles	Green synthesis	Spherical,<50 nm	TEM,EDS,SEM	-	[33]
	Si-Ganoderma lucidum nanoparticles	Green synthesis	200-300 nm	TEM,XRD,SAED	-	[34]
	CuO-Ganoderma lucidum nanoparticles	Green synthesis	Spherical,4-5 nm	UV-vis,TEM,FTIR,XRD,DLS	Antibacterial	[35]
Chemical method	Ganoderma lucidum polysaccharides as nanocarriers with main chains	Nanoprecipitation method	(54.76±3.72)nm	HPLC,TEM,DLS	Anticancer	[36]
		Nanoprecipitation method	60 nm	H-NMR,TEM	Drug carrier	[37]
		Nanoprecipitation method	Spherical,300 nm	FTIR,TEM,HNMR	Drug carrier	[38]
		Nanoprecipitation method	Spherical,190 nm	TEM,DLS	Drug carrier	[39]
	Ganoderma lucidum nanoemulsion	Emulsified solvent evaporation method	Spherical,50-200 nm	Zeta,TEM	-	[40]
	Nanoemulsion of Ganoderma spore oil as oil phase	Emulsified solvent evaporation method	Spherical,(141.92±3.38)nm	Cryo-SEM,Zeta	Enhance the immunity	[41]
	Nanoemulsion of Ganoderma lucidum polysaccharides in aqueous phase	Emulsification method	70.08±3.15 nm	DSC,PXRD,SEM	Drug carrier	[42]
		Emulsification method	Spherical,35-37 nm	HPLC,Zeta,DSC,PXRD,SEM	Drug carrier	[43]
		Emulsification method	Spherical,(54.23±1.02)nm	Zeta,AOR,Dt,SEM,TEM,DSC,PXRD	Anti-diabetes and anti-oxidation as a drug carrier	[44]
Physical method	Ganoderma lucidum nanoparticles	Machine crushing	500 nm	SEM	Inhibited HeLa cells	[45]

灵芝纳米的制备及应用研究进展

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王燕 ¹ , 秦慧妮 ¹ , 冯佳乐 ¹ , 刘艳丽 ² , 郭锐 ¹ , 李俊耀 ¹ , 纪丽莲 ¹ , 王桃云 ¹^,^*

中国药学杂志 | 综述 2025,60(2): 144-152

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中国药学杂志 | 综述 2025, 60(2): 144-152

灵芝纳米的制备及应用研究进展

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王燕¹, 秦慧妮¹, 冯佳乐¹, 刘艳丽², 郭锐¹, 李俊耀¹, 纪丽莲¹, 王桃云¹^,^*

作者信息

¹ 苏州科技大学化学与生命科学学院, 江苏苏州 215009

² 苏州大学药学院, 江苏苏州 215123

王燕,女,硕士研究生研究方向:生物纳米制备及活性研究

通讯作者:

*王桃云,男,博士,副教授,研究生导师研究方向:天然药化与生物材料研究 Tel:(0512)68418938

Advances in Preparation and Application of Ganoderma lucidum Nanoparticles

Yan WANG¹, Huini QIN¹, Jiale FENG¹, Yanli LIU², Rui GUO¹, Junyao LI¹, Lilian JI¹, Taoyun WANG¹^,^*

Affiliations

¹ School of Chemistry and Life Sciences, Suzhou University of Science and Technology, Suzhou 215009, China

² School of Pharmacy, Soochow University, Suzhou 215123, China

出版时间: 2025-01-22 doi: 10.11669/cpj.2025.02.006

文章导航

摘要

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灵芝(Ganoderma lucidum)是多孔菌科灵芝属真菌,是一种药食两用的珍贵药材,具有抗氧化、抗菌、抗肿瘤、抗炎及神经保护等多种生物活性。然而,由于灵芝不易溶解、生物利用率低、难以被人体吸收以及直接使用会增加肝损伤患者的肝脏负担等原因,灵芝的应用受到很大限制。近年来,为了提高灵芝的应用功效并扩大其运用范围,灵芝纳米化研究受到研究人员的广泛关注。笔者介绍了灵芝纳米的制备(包括生物法、化学法和物理法)及其在生物医药保健、环境、农业等领域的应用及作用机制,指出了现有相关研究存在的不足及今后的发展方向,为灵芝纳米的深入研究提供参考。

关键词

灵芝 / 纳米颗粒 / 制备方法 / 应用领域

Abstract

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Ganoderma lucidum is a fungus belonging to the genus Ganoderma in the family of Polyporaceae. As a precious medicinal herb which can be used for both medicine and food, it has various biological activities such as antioxidant, antibacterial, anti-tumor, anti-inflammatory, and neuroprotective properties. However, due to the difficulty in dissolution, low bioavailability, difficulty in absorption by the human body, and the increased burden on liver injury patients caused by direct use, the application of Ganoderma lucidum is greatly limited. In recent years, in order to improve the application efficiency of Ganoderma lucidum and expand its scope of application, the research on its nanoparticle size has received widespread attention from researchers. The article introduces the preparation of Ganoderma lucidum nanoparticles (including biological, chemical and physical methods) and their applications and mechanisms of action in different fields such as biomedicine, health care, environment and agriculture. It points out the shortcomings of existing related research and future development directions, and provides reference for in-depth research on Ganoderma lucidum nanoparticles.

Key words

Ganoderma lucidum / nanoparticle / preparation method / application area

引用本文

王燕, 秦慧妮, 冯佳乐, 刘艳丽, 郭锐, 李俊耀, 纪丽莲, 王桃云. 灵芝纳米的制备及应用研究进展. 中国药学杂志, 2025 , 60 (2) : 144 -152 . DOI: 10.11669/cpj.2025.02.006

Yan WANG, Huini QIN, Jiale FENG, Yanli LIU, Rui GUO, Junyao LI, Lilian JI, Taoyun WANG. Advances in Preparation and Application of Ganoderma lucidum Nanoparticles[J]. Chinese Pharmaceutical Journal, 2025 , 60 (2) : 144 -152 . DOI: 10.11669/cpj.2025.02.006

正文

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灵芝(Ganoderma lucidum)是多孔菌科灵芝属真菌,是一种珍贵的中草药,被誉为“中药之王”^[1],广泛分布于世界各地,全世界灵芝约有200种,中国约有105种。目前,已经发现灵芝中有400多种营养成分,主要包括灵芝多糖、灵芝三萜、蛋白质和生物碱等^[2]。现代药理学研究表明,灵芝具有抗氧化、免疫调节、抗神经退行性和抗糖尿病等药理活性^[3];同时临床报道灵芝具有抗癌^[4]、抗衰老^[5]、降血糖^[6]、保护神经^[7]、抗骨质疏松^[8]及免疫调节活性^[9]。然而,灵芝存在水中溶解度小、生物利用度低、人体无法完全吸收等缺点,在很大程度上降低了灵芝的药理活性,大大限制了灵芝的应用。

为了解决上述问题,研究人员利用灵芝直接或间接制备成纳米材料(统称灵芝纳米),以改善其溶解度,增强稳定性,提高利用性和靶向性,并延长体内药用时间,从而提高灵芝的功效,扩大其应用范围。近年来,灵芝的纳米化制备技术正逐步朝着环保友好的方向发展。同时,通过多种纳米化修饰方法,有效地实现了用少量灵芝达到最大药效的目标。这一进展为灵芝纳米在医疗卫生领域的应用开辟了新的途径,为疾病的预防和治疗提供了更为有效的策略。

笔者围绕当前灵芝纳米化研究的热点,对灵芝纳米的制备方法、应用领域及其作用机制研究进行了综述,为灵芝纳米的深入研究提供参考。

1 灵芝纳米制备

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纳米制备可分为“自上而下”和“自下而上”两类方法^[10](图1)。“自上而下”的方法是从较大的结构开始将其分解,直至纳米级,该类方法称为物理法,如研磨、高压均质^[11]和激光销蚀法^[12]等。“自下而上”的方法是从原子或者分子开始,组装成所需的纳米结构,它包括生物法、化学法^[13]。物理、化学方法操作较简单。生物法通常使用植物提取物、动物细胞组织或者细菌真菌制备合成金银铜铁等金属纳米颗粒,该类方法具有简单易行、绿色环保、产物纯度高、成本低等优点。灵芝纳米的制备也可以分为生物法、化学法和物理法。

1.1 生物法制备灵芝纳米

生物法是制造纳米材料的新兴纳米合成技术^[14],具有环保、高效、低成本、纯度高等^[15]优点。已经报道了利用植物^[16]、动物^[17]、细菌^[18]、真菌^[19]和生物衍生品^[20]生物合成纳米材料。其中,利用植物及其提取的生物活性成分合成纳米颗粒的过程相对简单且原料容易获得。灵芝含有很多活性化合物,包括氨基酸、酚类、蛋白质和多糖,可以用于胞内或胞外^[21]还原金属离子,制备出金属灵芝纳米(M-灵芝纳米),M-灵芝纳米是目前研究最多的灵芝纳米。灵芝的各种生物成分或组分,如菌丝体、酶、粗多糖或粉末,也可用于合成M-灵芝纳米^[22](图2)。Dandapat等^[23]报道了位于613、925、1681、2430和3606 cm^-1处吸收峰对应于单宁、皂苷、黄酮、生物碱类、酚类等生物活性物质,透射电镜(TEM)图像显示M-灵芝纳米被有机层覆盖,通过EDX光谱测定发现C、O、N等元素。灵芝纳米的粒径和应用效果,取决于反应时间、反应温度、化学试剂的浓度和溶液pH值。

1.2 化学法制备灵芝纳米

化学法是使用无机或有机还原剂合成纳米颗粒,制备过程中添加保护剂,如聚乙二醇、聚甲基丙烯酸甲酯等^[24],可防止纳米颗粒聚集。化学法制备灵芝纳米主要包括纳米沉淀法和乳化法。纳米沉淀法主要是指通过化学修饰灵芝多糖,使得灵芝多糖具有两亲性,在一定条件下装载疏水性药物并自组装成由灵芝为载体的纳米颗粒。乳化法主要是指利用灵芝孢子油作为油相或者灵芝多糖等活性化合物作为水相,制备出水包油型灵芝纳米乳液。

1.3 物理法制备灵芝纳米

物理法中常使用高剪切力或高压的均质机将大颗粒固体分解成更细、更均匀的纳米颗粒,该方法适用于工厂大规模批量生产^[25]。用于制备灵芝纳米的物理法包括机械研磨、高压均质等。

生物法制备灵芝纳米在经济性和安全性方面具有一定优势。这种方法相对环保,通常不需要使用有害化学品,降低了对环境的影响,也有利于产品的安全性。此外,生物法制备通常能够保留灵芝中的活性成分,但在实际应用中需要综合考虑生产成本、生产周期以及产品质量等因素。化学法制备则涉及化学合成或溶剂使用,能够精准控制合成颗粒大小和形貌,但对环境和人体健康不友好。物理法制备灵芝纳米操作简单,但通常耗时长且能耗高,可能导致灵芝结构改变和活性成分丢失。见表1。

2 灵芝纳米的应用

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2.1 生物医药保健领域的应用

2.1.1 抗氧化作用

抗氧化是指清除自然生理作用或衰老、过度运动、感染及体内有毒物质产生的有害活性氧(ROS)^[46]。体内ROS包括脂质自由基、烷氧基、过氧基等^[47]。细胞内抗氧化系统在可调节浓度下产生的ROS有助于血管舒张或调节免疫功能。然而,ROS自由基过量产生,尤其在衰老或不健康的情况下,就会损伤细胞,导致炎症、动脉硬化、关节炎、癌症等各种疾病^[48]。因此,清除自由基对于保护人体健康起着至关重要的作用。

灵芝纳米的抗氧化是灵芝纳米颗粒以内吞的方式进入细胞,因其粒径小、比表面积大^[49],能够提供足够的活性位点与自由基反应并抑制细胞氧化。Cai等^[50]发现灵芝介导的硒纳米比表面积大、活性位点多,对1,1-二苯基-2-三硝基苯肼(DPPH)有显著的清除作用,其清除能力约为维生素C的20%。Dai等^[51]使用荧光染料二氢乙锭和2',7'-二氯二氢荧光素二乙酸酯探针,发现灵芝纳米被内吞进入H9C2细胞,在肝脏中可逆转经X射线照射后总超氧化物歧化酶(T-SOD)和谷胱甘肽过氧化物酶(GSH-Px)含量下降,并使得丙二醛(MDA)含量下降,在120 min后开始抑制ROS生成,表现出较强抗氧化活性。

灵芝纳米的抗氧化机制主要表现在以下几个方面(图3):①从灵芝纳米中接受电子或质子,直接清除机体中的ROS^[52](包括

O 2 -

、·OH、ONOO^-);②灵芝纳米表层附着有黄酮、多酚及多糖^[52]等活性成分,增强了灵芝纳米的抗氧化活性;③通过增强机体抗氧化酶活性(SOD、CAT、GPx、GSH)^[53],间接发挥抗氧化作用,降低脂肪酸氧化的限速酶CPT-1酶含量^[54],从而抑制脂肪酸氧化;④通过调节信号通路(如JNK、XRCC1、γ-H₂A.X、AKT、ERK、MGMT、PARP等)来抑制机体氧化应激的发生,从而控制X射线诱导的ROS过量产生^[51]。

2.1.2 抗菌作用

灵芝可将银离子还原生成被灵芝封盖的银纳米(Ag-灵芝纳米)。Ag-灵芝纳米具有比单一的灵芝提取物或单质银更高的抗菌活性。抗菌效果的增强源于灵芝中还原性成分和银纳米颗粒之间的协同作用,通过不同的机制作用于微生物细胞,相互增强Ag-灵芝纳米抗菌活性,使得Ag-灵芝纳米的抗菌效果比单一物质作用时表现更出色^[55]。Milan等^[21]采用圆盘扩散法对肺炎克雷伯菌、大肠杆菌、伤寒沙门氏菌、枯草芽孢杆菌、蜡样芽孢杆菌和金黄色葡萄球菌进行抑菌活性测定,发现Ag-灵芝纳米对革兰阳性菌的抑制效果优于革兰阴性菌。Karwa等^[56]研究发现Ag-灵芝纳米与庆大霉素和链霉素等抗生素联用,抗生素中的羟基和氨基等活性基团与Ag-灵芝纳米之间的键合作用引起协同作用,提高了抗菌效果,其中对金黄色葡萄球菌抗菌效果最好。

灵芝纳米对不同菌株抗菌效果不同可能与微生物细胞壁和外膜有关^[57],也有可能与灵芝提取液或金属纳米的浓度有关。一方面,革兰阳性菌含有较厚的肽聚糖层,该层由多糖线性链构成,短肽作为交联键,产生刚性的细胞壁以保护其细胞器,但又因其缺乏外膜且肽聚糖具有渗透性,使得灵芝纳米更易进入细菌细胞内,使酶和蛋白质失活,与DNA结合,破坏代谢过程,抑制细菌的生长繁殖。另一方面,革兰阴性菌的细胞壁具有外膜,可作为渗透屏障,影响灵芝纳米的进入,从而降低其对革兰阴性菌的抗菌效果。

灵芝纳米的抑菌机制^[58]主要体现在以下几方面(图4):①黏附在细菌表面,使得M-灵芝纳米渗透到细胞中,导致生物分子的破坏和细胞内损伤;②M-灵芝纳米与细胞膜相互作用,促使金属离子和灵芝中活性物质与细胞DNA结合,破坏代谢过程,并抑制细菌增殖;③通过引发细胞氧化应激的ROS,诱导细胞病原性死亡;④细菌膜渗透性显著增加,使细胞不能通过质膜调节运输,最终导致细胞死亡。

2.1.3 抗炎作用

炎症是对刺激的防御反应,表现为红、肿、热、痛等症状。市面上出售的抗炎药会产生胃溃疡、出血、胃黏膜破裂等风险,且仅限用于治疗慢性炎症性疾病^[59]。纳米作为潜在的抗炎剂,具有较大的比表面积,更易阻断炎症增强剂等特点,为炎症疾病的治疗开辟了新的方向。

巨噬细胞通过释放NO、前列腺素E2(PGE2)、活性氧和细胞因子IL-1β,IL-6、肿瘤坏死因子-α(TNF-α),使生物体局部感染炎症。灵芝纳米的加入,可阻断NF-кB和抑制JNK1/2、p38MAPKs、COX-2信号通路的磷酸化,从而抑制促炎因子TNF-α、IL-1β、IL-6、IL-10、PGE2等mRNA的基因表达,减少iNOS和NO的产生^[60-61],抑制巨噬细胞增殖,最终抑制急慢性炎症。Tsai等^[62]用W/O乳化溶剂挥发法制备的灵芝纳米,为球形结构,粒径为184.5 nm,5 μg·mL^-1的该灵芝纳米是治疗角膜上皮细胞炎症的最佳浓度,能显著下调TNF-α、IL-1α、IL-8和MMP-3促炎细胞因子的基因表达量,提高正常细胞存活率,还能促进角膜创面愈合,减轻炎症反应。

2.1.4 抗癌作用

癌症是导致人类死亡的主要原因之一。传统治疗癌症的方法主要有放射治疗、手术、化疗、激素疗法、免疫疗法、骨髓移植、靶向治疗、冷冻消融、射频消融等,但这些方法对人体有副作用,且增加人体对药物的耐药性。近几十年间,纳米材料辅助癌症治疗颇有成效。Su等^[63]研发了灵芝复方丹皮酚纳米乳作为新型抗肺癌药物,提高药物的稳定性和包封率。Gao等^[45]将灵芝纳米化,增加在溶剂中暴露的表面积,提高溶剂提取量,有效抑制了宫颈癌Hela细胞增殖。Sabaratnam等^[22]发现Ag-灵芝纳米对MDA-MB-231人乳腺癌细胞有抑制作用并能诱导癌细胞膜渗漏,Kumar等^[64]采用MTT法、SCGE法、凋亡法和Mito-potential法研究发现被灵芝封盖的金纳米(Au-灵芝纳米)与化疗抗癌药物多柔比星的偶联,会产生协同效应,对MCF-7-dox耐药乳腺癌细胞有显著的抑制作用。

灵芝纳米抗癌作用机制通常是灵芝纳米进入癌细胞系,引起线粒体氧化应激,产生过量的ROS,诱导caspase活化,导致DNA链断开,引起IL-6、IL-12、IL-1β、TNF-α和IFN-γ的mRNA水平上调^[65]。与此同时,癌细胞的形态发生明显变化,如收缩、形状不规则、细胞质起泡、细胞内液泡形状的变化和染色质凝结等,最后导致癌细胞坏死,具体见图5。

2.1.5 降脂作用

肥胖症与体内甘油三酯过量有关,灵芝纳米可以通过促进甘油三酯降解或增强降血脂活性,从而降低体脂率。Krobthong等^[66]研究灵芝纳米在体外对3T3-L1脂肪细胞的脂解刺激活性,结果显示,52.34 μg·mL^-1的灵芝纳米能有效诱导细胞脂解,同时对人体正常细胞无毒。在蛋白质组学研究中发现,灵芝纳米通过下调TSSK5、SMU1、GRM7和上调KLC4蛋白表达来促进细胞脂质降解。在小鼠体内发现,服用灵芝纳米且结合适当运动后,肥胖小鼠的体质量远低于对照组^[67]。

2.1.6 抗糖尿病

Ranjith等^[68]对灵芝包覆银的纳米氧化锌颗粒(Ag-ZnO-灵芝纳米)进行体外研究,发现随着Ag-ZnO-灵芝纳米浓度的增大,对α-淀粉酶和α-葡萄糖苷酶抑制率显著增加。因此Ag-ZnO-灵芝纳米可用于制备有效的抗糖尿病药物。

2.1.7 药物运输

传统给药系统存在生物利用性差和剂量高,且在到达靶向作用位点前在肠道和血管系统的递送过程中部分药物就会降解的缺点,而纳米药物运输系统的出现成功解决了此类问题,它具有以下几个优点:①保护其纳米核心中的药物免受生物体液降解;②提高对特定组织的靶向效率;③控制药物对特定信号的释放。

Yao等^[69]利用电喷雾工艺将灵芝多糖负载在海藻酸钠微粒中。研究结果表明,在不同环境温度下,负载能力和封装效率均为23%和71%,并且在胃液环境(pH=1.7)中,灵芝纳米能够通过聚合链收缩,从而在酸性环境下保存灵芝多糖,并在进入肠道(pH=7.4)后快速释放药物。另外,Lee等^[70]通过氢键将灵芝提取物负载在纳米复合材料表面,以提高纳米材料的水分散性和稳定性。他们通过外部磁场控制灵芝纳米到达靶向位置,在该位置积聚并释放药物。同时Krobthong等^[66]将灵芝蛋白水解物用纳米脂质体包裹,诱导脂肪细胞甘油三酯的分解,增加甘油释放来影响脂肪细胞。在脂质体中,下调了TSSK5、SMU1_MOUSE、EIF3E基因,而KLC4基因的表达被上调。这些研究结果表明,灵芝纳米的应用有望解决传统给药系统的问题,提高药物的靶向性和释放效率。

2.2 环境领域的应用

2.2.1 降解有机污染物

基于灵芝纳米这一重要研究对象,近年来相关研究者在环境修复与污染治理领域取得了显著进展。研究发现,灵芝可以分泌出一种漆酶^[71],能够促进对染料的降解。Fan等^[72]将灵芝负载于磁性纳米中,发现仅10 mg灵芝纳米就能去除99%的靛蓝胭脂红,循环10次后仍保持75%的活性。更有研究者^[73]首次从灵芝中分离出酚类合成Au-灵芝纳米纳米颗粒,该物质表现出快速催化还原亚甲基蓝的能力,有效减少了环境污染。

2.2.2 催化作用

灵芝纳米具有大比表面积和独特的结构特性,可以作为高活性、高选择性的催化剂使用。Nguyen等^[74]利用微波辅助在短时间内绿色合成Au-灵芝纳米。添加少量的Au-灵芝纳米作为催化剂,使对硝基酚与硼氢化钠在短时间内快速发生氧化还原反应,生成4-硝基苯酚(C₆H₄NO^3·)离子,使其在400 nm处的峰强度迅速减弱,30 min内对硝基酚被完全还原。每次使用完的Au-灵芝纳米,可以通过洗涤、离心及干燥后,即可再次作为催化剂使用,重复使用4次后催化效率仍能达到100%。同样,Lai等^[75]采用水热法从灵芝中萃取出灵芝多糖,与四氯铂酸钾在60 ℃反应12 h,得到灵芝多糖-纳米铂团簇,由于粒径小(约2 nm)、比表面积大,在60 ℃、pH值为4.0时表现出的催化活性最高。

2.2.3 检测污染物

灵芝纳米具有很强的吸附能力,可以有效捕获环境中的重金属和有毒气体等,通过简单的判定方法,间接推算出环境中污染物含量。Nguyen等^[76]开发了一款对Fe³⁺高灵敏度的灵芝纳米传感器,仅通过颜色变化就能检测出水环境中的重金属离子,最低检出限为1.85 nmol·L^-1,与标准的AAS检测技术相比没有显著差异,且回收率高达99.5%~102.1%。ZnO-灵芝纳米对罗丹明6G和亚甲基蓝的检测线降至10^-7 mol·L^-1^[77],在处理水污染方面有较大的应用前景。

灵芝纳米除了可以监测水环境中的污染物,也可以监测有毒气体,TiO₂-灵芝纳米作为气体传感器^[78],可对氨气、硫化氢、二氧化碳、二氧化氮和氯气进行检测。对氯气的监测最为敏感,在150 ℃时表现出较高的气敏性,检出范围可从5至400 mg·L^-1。

2.3 农业领域的应用

2.3.1 纳米肥料

施用含氮和磷的肥料,最终会导致土壤环境恶化,而生物纳米肥料可作为化学肥料的可持续替代品,不仅利于植物吸收,且成本低、对环境影响小。灵芝绿色合成的纳米氧化锌首次被应用为纳米肥料^[79],研究发现低剂量合成下的纳米氧化锌为高度排列六方圆盘结构,显著促进家独行菜种子的萌发,显著增加了胚根、胚芽、鲜重和干重的量,增加了45%、41%、16%和33%,叶绿素和类胡萝卜素的含量也增加了,促进种子的萌发,节省了营养素的消耗,降低对环境的污染。为未来研究纳米肥料改善植物生长,提高作物产量的研究提供理论参考。

2.3.2 纳米农药

灵芝纳米能够更好地渗透和转用,提高农药利用率,较少的纳米农药使用量能够达到杀虫或增产效果,并降低对环境的负荷。Jogaiah等^[80]将Ag-灵芝纳米分别润湿番茄和草莓的叶子,在叶片上滴加5 mmol·L^-1的灰葡萄孢和胶孢炭疽菌真菌,在25 ℃的黑暗中孵化7 d。结果发现,未经Ag-灵芝纳米处理的番茄和草莓叶片出现完全坏死和叶片枯萎,而Ag-灵芝纳米处理后,在不影响番茄和草莓叶片形态下,防止真菌在水果叶片中的传播,为在纳米农药领域提供了新的思路。

2.4 其他领域的应用

生物纳米材料除了应用于生物医药保健领域、环境领域及农业领域以外,还可以用于生产抗菌织物及生物传感器(图6)。

2.4.1 抗菌织物

市场上含抗菌剂的纺织品会造成环境污染,如季铵盐类、卤代酚类等有机抗菌剂不耐热且有毒^[81],而灵芝纳米可作为抗菌剂用于生产的抗菌织物对环境安全无污染。Sneha-Paul等^[82]发现,浸有1.57%灵芝纳米银的棉织物对三种病原菌(变形杆菌、金黄色链球菌和假单胞菌)均有较强的抗菌活性,无明显的细菌生长,因此被用作创面的抗菌敷料。

2.4.2 生物传感器

灵芝纳米由于其特殊的物理化学性质,可以用作敏感材料制备生物传感器。灵芝中分离出的漆酶通过共价键固定在铜纳米/壳聚糖/羧基化多壁碳纳米管/聚苯胺修饰的金电极^[83]上,形成灵芝纳米复合材料,是一种高灵敏度多酚生物传感器。在pH=6.0(0.1 mol·L^-1乙酸盐缓冲液)和35 ℃下4 s内就可获得检测结果。该灵芝纳米生物传感器可在7个月内使用300次,稳定性非常好,可应用于对茶、酒精饮料和药剂中的多酚含量进行测定。Liu等^[84]通过灵芝多糖还原和功能化氧化石墨烯来制备灵芝纳米酶,具有优异的过氧化物酶特性,用于L-半胱氨酸的检测,检出限为0.1 μmol·L^-1,检出范围为2~30 μmol·L^-1。该灵芝纳米可应用于检测血清中L-半胱氨酸。

3 结论与展望

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灵芝是一种名贵中药材,具有抗炎、抗氧化、抗肿瘤等广泛的药理活性。但由于溶解度差和生物利用率低等原因限制了临床应用。而将灵芝纳米化能很好地解决以上问题。目前,相关研究者通过生物法、化学法和物理法成功制备出灵芝纳米,具有增强生物利用性、提高生物活性、改善药物稳定性、减少剂量和副作用、增强靶向性、促进药物组合疗法等优势。研究者们正探索灵芝纳米在生物医学保健应用及作用机制,同时为灵芝纳米在环境、现代农业、抗菌织物、生物传感器等领域的应用开辟新方向。

目前,灵芝纳米在生物医学保健应用领域的研究仍处于基础阶段,许多问题仍需进一步研究。研究人员需要深入探讨多元化制备灵芝纳米产生的潜在毒性,包括长期暴露的影响、生物相容性和安全等方面,以确保其在临床应用中的安全性;致力于优化灵芝纳米作为药物递送系统的性能,包括提高靶向性、降低药物剂量、延长药物在体内的停留时间等方面;同时还需要通过大规模临床研究,验证灵芝纳米在治疗特定疾病中的有效性和安全性,为其未来在临床实践中的应用提供更多证据支持。此外,灵芝纳米在环境、农业及抗菌织物等其他领域的应用,需考虑生产成本、实际应用价值以及潜在的风险,以确保其在实际应用中具有可持续性和经济性。灵芝纳米在多个应用领域取得了重大进展,不过在食品工业应用领域存在巨大的研究空白,研究人员可以将灵芝纳米作为保健食品的添加剂,探究对食品的抗氧化、抗菌、保鲜等功能的影响,同时也需要考虑制备成本以及毒理试验评估。为了推动灵芝纳米在各个领域的研究和应用,研究人员可以朝着低能耗、大规模生产方向发展,以实现其在更大范围实际应用的可能性。

基金

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国家自然科学基金面上项目资助(82073912)

参考文献

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文献

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参考文献引证文献

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2025年第60卷第2期

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doi: 10.11669/cpj.2025.02.006

接收时间：2024-05-09
首发时间：2025-11-08
出版时间：2025-01-22

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收稿日期：2024-05-09

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国家自然科学基金面上项目资助(82073912)

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¹ 苏州科技大学化学与生命科学学院, 江苏苏州 215009

² 苏州大学药学院, 江苏苏州 215123

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*王桃云,男,博士,副教授,研究生导师研究方向:天然药化与生物材料研究 Tel:(0512)68418938

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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Methods	Nanoparticles	Preparation	Morphology and size	Characterization methods	Application	Reference
Biological method	Au-Ganoderma lucidum nanoparticles	Green synthesis	Spherical,oval and irregular, 1-100 nm	UV-Vis,XRD,EDX,TEM	Inhibited HT-29 colon cancer cell line	[26]
	Ag-Ganoderma lucidum nanoparticles	Green synthesis	Spherical,9-21 nm	XPS,XRD,TEM,UV-Vis,FTIR	Antioxidant and antibacterial	[27]
		Green synthesis	Spherical,11-16 nm	UV-Vis,XRD,FTIR,SEM,TEM	Antioxidant,antibacterial and inhibited the human epidermic carcinoma cancer cell line	[28]
		Green synthesis	Spherical,23-58 nm	UV-Vis,XRD,SEM,FTIR	Antioxidant,antibacterial and inhibited the breast cancer cell line-MDA-MB-231	[29]
		Green synthesis	Spherical,(133.0±0.361)nm	UV-Vis,FTIR,Zeta,SEM	Antibacterial	[30]
		Green synthesis	Spherical,200 nm	TEM,DLS,XRF	-	[31]
	ZnO-Ganoderma lucidum nan- oparticles	Green synthesis	“Petals”,50-200 nm	XRD,TEM,UV-Vis,PL	Detect Rhodamine	[32]
	Se-Ganoderma lucidum nanoparticles	Green synthesis	Spherical,<50 nm	TEM,EDS,SEM	-	[33]
	Si-Ganoderma lucidum nanoparticles	Green synthesis	200-300 nm	TEM,XRD,SAED	-	[34]
	CuO-Ganoderma lucidum nanoparticles	Green synthesis	Spherical,4-5 nm	UV-vis,TEM,FTIR,XRD,DLS	Antibacterial	[35]
Chemical method	Ganoderma lucidum polysaccharides as nanocarriers with main chains	Nanoprecipitation method	(54.76±3.72)nm	HPLC,TEM,DLS	Anticancer	[36]
		Nanoprecipitation method	60 nm	H-NMR,TEM	Drug carrier	[37]
		Nanoprecipitation method	Spherical,300 nm	FTIR,TEM,HNMR	Drug carrier	[38]
		Nanoprecipitation method	Spherical,190 nm	TEM,DLS	Drug carrier	[39]
	Ganoderma lucidum nanoemulsion	Emulsified solvent evaporation method	Spherical,50-200 nm	Zeta,TEM	-	[40]
	Nanoemulsion of Ganoderma spore oil as oil phase	Emulsified solvent evaporation method	Spherical,(141.92±3.38)nm	Cryo-SEM,Zeta	Enhance the immunity	[41]
	Nanoemulsion of Ganoderma lucidum polysaccharides in aqueous phase	Emulsification method	70.08±3.15 nm	DSC,PXRD,SEM	Drug carrier	[42]
		Emulsification method	Spherical,35-37 nm	HPLC,Zeta,DSC,PXRD,SEM	Drug carrier	[43]
		Emulsification method	Spherical,(54.23±1.02)nm	Zeta,AOR,Dt,SEM,TEM,DSC,PXRD	Anti-diabetes and anti-oxidation as a drug carrier	[44]
Physical method	Ganoderma lucidum nanoparticles	Machine crushing	500 nm	SEM	Inhibited HeLa cells	[45]

Methods

Nanoparticles

Preparation

Morphology and size

Characterization methods

Application

Reference

Biological method

Au-Ganoderma lucidum nanoparticles

Green synthesis

Spherical,oval and irregular,
1-100 nm

UV-Vis,XRD,EDX,TEM

Inhibited HT-29 colon cancer cell line

[26]

Ag-Ganoderma lucidum nanoparticles

Green synthesis

Spherical,9-21 nm

XPS,XRD,TEM,UV-Vis,FTIR

Antioxidant and antibacterial

[27]

Green synthesis

Spherical,11-16 nm

UV-Vis,XRD,FTIR,SEM,TEM

Antioxidant,antibacterial and inhibited the human epidermic carcinoma cancer cell line

[28]

Green synthesis

Spherical,23-58 nm

UV-Vis,XRD,SEM,FTIR

Antioxidant,antibacterial and inhibited the breast cancer cell line-MDA-MB-231

[29]

Green synthesis

Spherical,(133.0±0.361)nm

UV-Vis,FTIR,Zeta,SEM

Antibacterial

[30]

Green synthesis

Spherical,200 nm

TEM,DLS,XRF

[31]

ZnO-Ganoderma lucidum nan-
oparticles

Green synthesis

“Petals”,50-200 nm

XRD,TEM,UV-Vis,PL

Detect Rhodamine

[32]

Se-Ganoderma lucidum
nanoparticles

Green synthesis

Spherical,<50 nm

TEM,EDS,SEM

[33]

Si-Ganoderma lucidum nanoparticles

Green synthesis

200-300 nm

TEM,XRD,SAED

[34]

CuO-Ganoderma lucidum nanoparticles

Green synthesis

Spherical,4-5 nm

UV-vis,TEM,FTIR,XRD,DLS

Antibacterial

[35]

Chemical method

Ganoderma lucidum polysaccharides as nanocarriers with main chains

Nanoprecipitation method

(54.76±3.72)nm

HPLC,TEM,DLS

Anticancer

[36]

Nanoprecipitation method

60 nm

H-NMR,TEM

Drug carrier

[37]

Nanoprecipitation method

Spherical,300 nm

FTIR,TEM,HNMR

Drug carrier

[38]

Nanoprecipitation method

Spherical,190 nm

TEM,DLS

Drug carrier

[39]

Ganoderma lucidum nanoemulsion

Emulsified solvent evaporation method

Spherical,50-200 nm

Zeta,TEM

[40]

Nanoemulsion of Ganoderma spore oil as oil phase

Emulsified solvent evaporation method

Spherical,(141.92±3.38)nm

Cryo-SEM,Zeta

Enhance the immunity

[41]

Nanoemulsion of Ganoderma lucidum polysaccharides in aqueous phase

Emulsification method

70.08±3.15 nm

DSC,PXRD,SEM

Drug carrier

[42]

Emulsification method

Spherical,35-37 nm

HPLC,Zeta,DSC,PXRD,SEM

Drug carrier

[43]

Emulsification method

Spherical,(54.23±1.02)nm

Zeta,AOR,Dt,SEM,TEM,DSC,PXRD

Anti-diabetes and anti-oxidation as a drug carrier

[44]

Physical method

Ganoderma lucidum nanoparticles

Machine crushing

500 nm

SEM

Inhibited HeLa cells

[45]