CN108434463A - 一种采用纳米探针示踪颈部深层***及脑膜***的方法 - Google Patents
一种采用纳米探针示踪颈部深层***及脑膜***的方法 Download PDFInfo
- Publication number
- CN108434463A CN108434463A CN201810240176.2A CN201810240176A CN108434463A CN 108434463 A CN108434463 A CN 108434463A CN 201810240176 A CN201810240176 A CN 201810240176A CN 108434463 A CN108434463 A CN 108434463A
- Authority
- CN
- China
- Prior art keywords
- nano
- probe
- neck
- meninx
- deep layer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000523 sample Substances 0.000 title claims abstract description 49
- 210000001165 lymph node Anatomy 0.000 title claims abstract description 39
- 238000000034 method Methods 0.000 title claims abstract description 20
- 239000000700 radioactive tracer Substances 0.000 title claims abstract description 14
- 210000002751 lymph Anatomy 0.000 claims abstract description 12
- 210000001365 lymphatic vessel Anatomy 0.000 claims abstract description 10
- 239000007850 fluorescent dye Substances 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 6
- 230000001926 lymphatic effect Effects 0.000 claims abstract description 5
- 239000000463 material Substances 0.000 claims abstract description 5
- 238000010276 construction Methods 0.000 claims abstract description 3
- 230000000694 effects Effects 0.000 claims abstract description 3
- 229920001992 poloxamer 407 Polymers 0.000 claims abstract description 3
- 238000002347 injection Methods 0.000 claims description 7
- 239000007924 injection Substances 0.000 claims description 7
- 239000010954 inorganic particle Substances 0.000 claims description 6
- 150000003384 small molecules Chemical class 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 239000002096 quantum dot Substances 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052710 silicon Inorganic materials 0.000 claims description 2
- 239000010703 silicon Substances 0.000 claims description 2
- 240000007594 Oryza sativa Species 0.000 claims 1
- 235000007164 Oryza sativa Nutrition 0.000 claims 1
- 235000013339 cereals Nutrition 0.000 claims 1
- 150000002475 indoles Chemical class 0.000 claims 1
- 235000009566 rice Nutrition 0.000 claims 1
- 238000011160 research Methods 0.000 abstract description 10
- 210000004324 lymphatic system Anatomy 0.000 abstract description 8
- 239000002105 nanoparticle Substances 0.000 abstract description 6
- 210000004556 brain Anatomy 0.000 abstract description 4
- 210000001519 tissue Anatomy 0.000 abstract description 4
- 238000001514 detection method Methods 0.000 abstract description 3
- 230000001575 pathological effect Effects 0.000 abstract description 3
- 239000011258 core-shell material Substances 0.000 abstract 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 8
- 239000002245 particle Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 3
- 210000004907 gland Anatomy 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 238000002386 leaching Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 229910021642 ultra pure water Inorganic materials 0.000 description 3
- 239000012498 ultrapure water Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 2
- 229960004657 indocyanine green Drugs 0.000 description 2
- 210000003563 lymphoid tissue Anatomy 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000011725 BALB/c mouse Methods 0.000 description 1
- -1 Cy5 Substances 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 201000007455 central nervous system cancer Diseases 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000009940 knitting Methods 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003376 silicon Chemical class 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0032—Methine dyes, e.g. cyanine dyes
- A61K49/0034—Indocyanine green, i.e. ICG, cardiogreen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0032—Methine dyes, e.g. cyanine dyes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0054—Macromolecular compounds, i.e. oligomers, polymers, dendrimers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0065—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle
- A61K49/0067—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle quantum dots, fluorescent nanocrystals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
- A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Nanotechnology (AREA)
- Materials Engineering (AREA)
- Inorganic Chemistry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
本发明属于纳米探针技术领域,具体涉及了一种采用纳米技术示踪深层颈部***及脑膜***的方法,所述方法以聚乙交酯丙交酯和普朗尼克F127为主要原料构建而成的核‑壳纳米颗粒作为模型纳米载药***(粒径20~50 nm),包载近红外荧光染料Cy5构成纳米探针。在右侧颈部皮下注射该纳米探针后,纳米探针通过组织局部的淋巴引流作用富集至颈部浅表***、颈部深层***和腋下***,其中颈部深层***与脑膜***直接相连。因此,纳米探针能够快速地传输至脑膜***,用于颈部深层***及脑膜***的实时成像示踪,为纳米颗粒在颈部的淋巴传输研究及脑部淋巴***的生理病理研究提供简单直接的检测手段。
Description
技术领域
本发明涉及纳米探针技术领域,具体地,涉及一种采用纳米探针示踪颈部深层***及脑膜***的方法。
背景技术
淋巴***是独立于血液循环***的另一套液体网状循环***,包括淋巴组织、***和淋巴液,是血液循环***的重要补充,对机体的免疫反应、内稳态和营养输送具有重要的意义。研究表明,淋巴***对疾病的发生发展具有重要影响。例如,恶性肿瘤在发生组织转移前,通常会浸润到原发部位周围的***。因此,通过对淋巴***进行显影成像来研究淋巴***的结构与生理功能,对疾病的防治尤为重要。
针对人体淋巴***的研究已较为透彻,然而对中枢神经***淋巴组织的研究尚处于起步阶段。Louveau等在2015年首次阐明中枢神经也具有淋巴***,脑膜***与颈部深层***直接相连且一直通向与大脑皮层附近的硬脑膜。这一重大发现填补了中枢神经淋巴***的空白,但目前仍没有确切的证据能够呈现中枢神经***的完整结构。
中枢神经***退行性疾病和癌症是目前最难攻克的疾病难题,发现和阐明中枢神经***的***构对疾病的诊疗和发生机理研究具有重要意义。
发明内容
本发明的目的是为了克服现有技术的上述不足,提供一种采用纳米探针示踪颈部深层***及脑膜***的方法,通过采用纳米技术对颈部***及脑膜***进行实时的荧光示踪,阐明两者之间相互联通及内部液体流动的关系,为纳米颗粒在颈部的淋巴传输研究及脑部淋巴***的生理病理研究提供简单、直观、实时、高效的检测手段,也为中枢神经***疾病的研究提供技术支持。
为了实现上述目的,本发明是通过以下方案予以实现的:
一种采用纳米技术示踪深层颈部***及脑膜***的方法,所述方法采用以聚乙交酯丙交酯和普朗尼克F127为主要原料构建而成的纳米载药***包载近红外荧光染料Cy5,制备了一种具有近红外荧光性质的纳米荧光探针;右侧颈部皮下注射该纳米荧光探针后24小时,纳米探针通过淋巴引流作用富集至颈部浅表***、颈部深层***和腋下***并达到最高剂量;颈部深层***与脑膜***直接相连,所述纳米探针能够快速传输到脑膜***,最终用于颈部深层***及脑膜***的实时成像示踪。
本发明首先制备了可包载Cy5、量子点等荧光染料的纳米探针,其制备方法如下:以聚乙交酯丙交酯(PLGA)、二硬脂酰磷脂酰乙醇胺-聚乙二醇-马来酰亚胺(DSPE-PEG)、普朗尼克F127(PF127)和荧光染料为原料,其中PLGA和Cy5溶于乙腈、二甲基亚砜等极性较强的有机溶剂中作为有机相,PF127和DSPE-PEG溶于超纯水作为水相。制备方法是快速纳米沉淀法,具体步骤为:①PLGA溶于极性有机溶剂中,浓度为1 ~ 10 mg/mL,荧光染料以合适浓度溶于其中,混合均匀;②PF-127溶于超纯水中,浓度为1 ~ 20 mg/mL,DSPE-PEG以合适浓度溶于其中,混合均匀;③PLGA/荧光染料的混合溶液作为通道1,PF127/DSPE-PEG的混合溶液作为通道2,超纯水作为通道3和通道4,将液体以一定流速挤压至多通道旋涡混合器中进行溶剂交换,通过快速纳米沉淀原理得到带有杂质的纳米探针溶液;④对上述溶液进行透析,除去有机溶剂和游离分子,得到纯化的纳米探针。上述制备技术及装置记载在本发明人同时提交的发明1专利中。
优选的,通道1和2的液体流速为1 ~ 15 mL/min,通道3和4的液体流速为5 ~ 50mL/min;
优选的,纳米探针的粒径大小为20 ~ 50 nm;
优选的,纳米探针的表面带负电荷。
所述纳米探针的具体特征为:①PLGA构成疏水内核,用于包载Cy5、Cy7和吲哚菁绿等有机的荧光染料,或者金属量子点、上转换材料和金属掺杂的硅量子点等无机颗粒;②PF127和DSPE-PEG构成亲水的外壳,使纳米探针表面为负电荷;③纳米颗粒的粒径大小为20~ 50 nm,体系稳定,颗粒表面带负电荷,有利于纳米探针富集至周围***,对颈部深层***及脑膜***的荧光成像更清晰。
优选地,所述纳米探针所包裹的荧光探针为有机荧光小分子或无机颗粒。
更优选地,所述有机荧光小分子为Cy5、Cy7和吲哚菁绿。
更优选地,所述无机颗粒为金属量子点、上转换材料和金属掺杂的硅量子点等无机颗粒。
优选地,所述纳米探针的注射部位是颈部附近位置,注射方式为皮下注射。
本发明其次通过皮下注射的方式将纳米探针注射至小鼠的右侧颈部皮下,通过对注射部位周围***和***的荧光强度、药物含量进行了跟踪监测,确定了纳米探针以最大剂量富集至颈部深层***及脑膜***的时间点,确立了一种分辨率高的、活体实时观测颈部深层***及脑膜***的新手段,为研究中枢神经***的药物递送及疾病发生发展提供技术支持。
本发明还请求保护所述方法在活体动物的局部***和***的实时成像示踪中的应用。
与现有技术相比,本发明具有以下有益效果:
本发明方法中所述纳米探针能够快速地传输至脑膜***,用于颈部深层***及脑膜***的实时成像示踪,为纳米颗粒在颈部的淋巴传输研究及脑部淋巴***的生理病理研究提供简单直接的检测手段。
附图说明
图1为包载Cy5的纳米探针(CNP)的粒径分布及TEM图像。
图2为颈部皮下注射CNP后颈部深层***及脑膜***的实时成像分析。
图3为颈部皮下注射CNP后第12小时、24小时和48小时,CNP在注射部位周围相关***(LN)的药物富集量。
具体实施方式
下面结合说明书附图及具体实施例对本发明作出进一步地详细阐述,所述实施例只用于解释本发明,并非用于限定本发明的范围。下述实施例中所使用的试验方法如无特殊说明,均为常规方法;所使用的材料、试剂等,如无特殊说明,为可从商业途径得到的试剂和材料。以下实施例中所涉及制剂来源如下:
PLGA、PF127 、Cy5购自Simga-Aldrich生物试剂公司,乙腈购自广州化学试剂公司,实验BLAB/c小鼠购自广东实验动物中心。
实施例1 包载Cy5的纳米探针的制备及表征
本实施例通过优化水相/有机相的配比和各个通道的液体流速,最终制备了粒径大小为42.4 nm,表面电位为-21.4 mV的纳米探针,具体实施步骤如下:①取6 mg PLGA,0.9 mgCy5溶于3 mL有机溶剂乙腈中,漩涡振荡混匀;15 mg PF127和1 mg DSPE-PEG溶于3 mL超纯水中,振荡混匀;②含有PLGA和ICG的乙腈溶液通过通道1(流速10 mL/min),含有PF127和DSPE-PEG的水溶液通过通道2(流速10 mL/min),12 mL超纯水分别通过通道3和4(流速为40mL/min),输送至多通道旋涡混合器中进行高速混合和溶剂交换,得到未纯化的纳米颗粒;③使用截留分子量为10kD的透析袋对颗粒溶液进行透析,即得纯化的包载Cy5的纳米探针CNP,结果如图1所示。
实施例2 注射纳米探针CNP后颈部深层***及脑膜***的实时成像
本实施例采用实施例1中制备而成的纳米探针(Cy5浓度为200 μg/mL),在BALB/c小鼠的右侧颈部皮下注射后,通过外科手术暴露小鼠的颈部深层***及脑膜***,使用活体共聚焦显微镜实时观察其结构及药物浓度变化。集体实施步骤如下:①异氟烷麻醉小鼠,在小鼠右侧颈部颈骨附近皮下注射纳米探针CNP 0.2 mL,使得小鼠接受的探针剂量为2mg/kg;②剪开小鼠颈部皮肤,钝性分离小鼠颈部肌肉组织,暴露颈部深层***及其附近相连的脑膜***;③利用Cy5在650-700 nm具有的荧光信号,使用尼康活体共聚焦显微镜对颈部深层***及其附近相连的脑膜***进行实时成像,成像监测时间为CNP注射后2小时到8小时之间,并对其间CNP在***和***的富集量进行荧光半定量,结果如图2所示。
实施例3 纳米探针CNP不同时间点在周围***的剂量
本实施例旨在探究纳米探针在颈部深层***达到最高剂量富集的时间点,集体实施步骤如下:①取小鼠12只,随机分为4组,每组3只;②取其中一组小鼠作为空白对照组,断颈处死小鼠后,摘取小鼠的颈部浅表***、颈部深层***、左侧腋窝***、右侧腋窝***各一对,组织匀浆破碎,多功能酶标仪检测各个样品在650 nm处的光吸收值;③其余3组小鼠均注射0.2 mL CNP,在12小时、24小时和48小时各处死一组小鼠,同样摘取每组小鼠的颈部浅表***、颈部深层***、左侧腋窝***、右侧腋窝***各一对,进行组织匀浆破碎,多功能酶标仪检测各个样品在650 nm处的光吸收值;④绘制CNP的浓度-吸收值标准曲线,通过曲线确定每组***中的CNP含量,结果如图3所示,第24小时CNP在小鼠颈部深层***的富集剂量最高,为活体成像示踪颈部深层***及脑膜***的最佳时间点。
Claims (7)
1.一种采用纳米技术示踪深层颈部***及脑膜***的方法,其特征在于,所述方法采用以聚乙交酯丙交酯和普朗尼克F127为主要原料构建而成的纳米载药***包载近红外荧光染料Cy5,制备了一种具有近红外荧光性质的纳米荧光探针;右侧颈部皮下注射该纳米荧光探针后24小时,纳米探针通过淋巴引流作用富集至颈部浅表***、颈部深层***和腋下***并达到最高剂量;颈部深层***与脑膜***直接相连,所述纳米探针能够快速传输到脑膜***,最终用于颈部深层***及脑膜***的实时成像示踪。
2.根据权利要求1所述的方法,其特征在于,所述纳米探针所包裹的荧光探针为有机荧光小分子或无机颗粒。
3.根据权利要求2所述的方法,其特征在于,所述有机荧光小分子为Cy5、Cy7和吲哚菁绿。
4.根据权利要求2所述的方法,其特征在于,所述无机颗粒为金属量子点、上转换材料和金属掺杂的硅量子点等无机颗粒。
5. 根据权利要求1所述的方法,其特征在于,所述纳米探针的粒径在20 ~ 50 nm,表面电位为负电荷。
6.根据权利要求1所述的方法,其特征在于,所述纳米探针的注射部位是颈部附近位置,注射方式为皮下注射。
7.权利要求1至6任一项所述方法在活体动物的局部***和***的实时成像示踪中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810240176.2A CN108434463B (zh) | 2018-03-22 | 2018-03-22 | 一种采用纳米探针示踪颈部深层***及脑膜***的方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810240176.2A CN108434463B (zh) | 2018-03-22 | 2018-03-22 | 一种采用纳米探针示踪颈部深层***及脑膜***的方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN108434463A true CN108434463A (zh) | 2018-08-24 |
CN108434463B CN108434463B (zh) | 2021-06-08 |
Family
ID=63196185
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810240176.2A Active CN108434463B (zh) | 2018-03-22 | 2018-03-22 | 一种采用纳米探针示踪颈部深层***及脑膜***的方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN108434463B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113368384A (zh) * | 2021-06-21 | 2021-09-10 | 温州医科大学慈溪生物医药研究院 | 脂质体电渗助导的大分子药物入脑的递送*** |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103623430A (zh) * | 2013-11-28 | 2014-03-12 | 郑州大学 | 一种基于聚乳酸-羟基乙酸共聚物的靶向共载药物传递***纳米粒的制备方法及应用 |
CN106166141A (zh) * | 2016-09-11 | 2016-11-30 | 复旦大学 | 一种用于肿瘤成像与治疗的多功能复合纳米药物及其制备方法 |
-
2018
- 2018-03-22 CN CN201810240176.2A patent/CN108434463B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103623430A (zh) * | 2013-11-28 | 2014-03-12 | 郑州大学 | 一种基于聚乳酸-羟基乙酸共聚物的靶向共载药物传递***纳米粒的制备方法及应用 |
CN106166141A (zh) * | 2016-09-11 | 2016-11-30 | 复旦大学 | 一种用于肿瘤成像与治疗的多功能复合纳米药物及其制备方法 |
Non-Patent Citations (3)
Title |
---|
D.A. RAO ET AL: "Effect of size and surface properties of biodegradable PLGA-PMA: PLA:PEG nanoparticles on lymphatic uptake and retention in rats", 《JOURNAL OF CONTROLLED RELEASE》 * |
HONGKEE SAH ET AL: "Concepts and practices used to develop functional PLGA-based nanoparticulate systems", 《INTERNATIONAL JOURNAL OF NANOMEDICINE》 * |
JYOTHI U. MENON ET AL: "Effects of surfactants on the properties of PLGA nanoparticles", 《JOURNAL OF BIOMEDICAL MATERIALS RESEARCH A》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113368384A (zh) * | 2021-06-21 | 2021-09-10 | 温州医科大学慈溪生物医药研究院 | 脂质体电渗助导的大分子药物入脑的递送*** |
Also Published As
Publication number | Publication date |
---|---|
CN108434463B (zh) | 2021-06-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
An et al. | Rationally assembled albumin/indocyanine green nanocomplex for enhanced tumor imaging to guide photothermal therapy | |
CN105056233B (zh) | 具有近红外光热和体内荧光成像特性的多功能介孔二氧化硅纳米粒及其制备方法和应用 | |
CN106139144B (zh) | 一种具有协同抗肿瘤特性的透明质酸修饰的金-碳纳米球及其制备方法与应用 | |
CA2733963C (en) | Encapsulation of lipophilic or amphiphilic therapeutic agents in nano-emulsions | |
JP2001501931A (ja) | 蛋白質安定化した薬理学的活性薬剤、その製造方法およびその使用方法 | |
Chang et al. | Ultrasound mediated destruction of multifunctional microbubbles for image guided delivery of oxygen and drugs | |
US11364312B2 (en) | Platinum sulfide protein nanoparticle having near-infrared photothermal effect and multimodal imaging function, preparation method therefor and application thereof | |
WO2009074274A1 (de) | Funktionalisierte, feste polymernanopartikel enthaltend epothilone | |
CN109771391A (zh) | 血小板膜包被的阿霉素-吲哚菁绿仿生纳米颗粒及其用途 | |
CN111888336B (zh) | 碳酸钙聚(乳酸-羟基乙酸)复合物微粒及其制备和应用 | |
CN110893237B (zh) | 铜钯合金纳米颗粒和自噬抑制剂在制备基于光热效应杀伤肿瘤的药物或试剂盒中的应用 | |
Lou et al. | A small-molecule based organic nanoparticle for photothermal therapy and near-infrared-IIb imaging | |
CN108324955A (zh) | 一种超小硫化铜负载的中空介孔硅靶向纳米载药复合物的制备方法 | |
CN108671231A (zh) | 一种用于肿瘤光热增效治疗和超声成像的多功能纳米载体及制备方法 | |
CN113521311B (zh) | 一种具有肿瘤靶向功能的双模态成像指导的聚合物囊泡及其制备方法和应用 | |
CN108434121B (zh) | 一种双层核壳结构分子载体 | |
Wang et al. | Mesoporous silica nanoparticles combined with MoS 2 and FITC for fluorescence imaging and photothermal therapy of cancer cells | |
CN109674764B (zh) | 一种抗肿瘤磁性载药杂化纳米胶囊及其制备方法 | |
KR102027311B1 (ko) | 염증성 비정상 조직 또는 종양 조직의 선택적 염색이 가능한 나노 진단 제제의 제조 방법 | |
CN108434463A (zh) | 一种采用纳米探针示踪颈部深层***及脑膜***的方法 | |
EP3682899A1 (en) | Compound amphiphilic peptide nanomicelle, preparation and use thereof | |
CN105999267A (zh) | 二硫化钼纳米点/聚苯胺纳米杂化物及制备方法及应用 | |
CN108721321A (zh) | 一种肿瘤靶向的纳米诊疗剂、其制备方法及其用途 | |
Zhang et al. | Nanoplaform based on ultra-small Au regulating phototoxicity and fluorescence off–on function of Ag2S for multi-modal diagnosis and treatment of tumor | |
CN105477020A (zh) | 基于蟾酥提取物的抗脑胶质瘤药物及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |