超顺磁金纳米壳复合颗粒的粒径调控及其诊疗应用

doi:10.15541/jim20150077

摘要/Abstract

摘要：

利用原位还原-种子生长法制备了超顺磁金纳米壳复合颗粒(SGNs), 研究了其粒径调控的方法并对其体外/体内磁共振成像(MRI)和光热治疗(PT)性能进行了测试。结果表明, 通过改变Fe₃O₄的加入量可方便地调控SGNs的粒径, 并成功制备了粒径分别为100、150和200 nm的SGNs复合颗粒。这些不同粒径的纳米复合颗粒均具有规则的球形形貌、较窄的粒径分布和单分散性。经巯基-聚乙二醇(SH-PEG)修饰后, 不同粒径的复合颗粒(SGNs-PEG)均表现出较强的MRI成像和光热转换能力。其中, 粒径为150 nm的复合颗粒对808 nm激光具有最强的吸收能力和光热转换效率, 体外和体内可升高温度分别达37 ℃和25 ℃, 同时具有较优异的MRI成像造影能力。因此, 在MDA-MB-435荷瘤小鼠肿瘤部位注射该复合颗粒后, 可先对肿瘤部位进行很好的成像诊断, 再利用激光照射通过光热转换有效地杀灭肿瘤细胞, 这为实现肿瘤诊疗的一体化提供了可能。

关键词: 四氧化三铁, 金纳米壳, 复合颗粒, 光热治疗, 磁共振成像

Abstract:

Superparamagnetic gold nanocomposites (SGNs), which have great potential in magnetic resonance imaging (MRI) and photothermal therapy (PT) on cancer, have been successfully synthesized via the in-situ reduction and the following seed-mediated growth route. It is found that the dimension of SGNs could be facilely tuned by changing the encapsulation amount of Fe₃O₄/tetrahydrofuran solution, and SGNs with diameters of 100, 150 and 200 nm were thus obtained. The as-synthesized SGNs present regularly spherical morphology, narrow size distributions and monodispersity in aqueous solutions. It is revealed that SGNs modified with SH-PEG are capable for simultaneous MRI and photothermal therapy. Especially, SGNs with average diameter of 150 nm exhibit the strongest absorption capacity and highest photothermal conversion efficiency with 808 nm laser. The temperatures in vitro and in vivo were increased by 37 ℃ and 25 ℃, respectively. Therefore, it is hopeful that tumor can be imaged well and killed efficiently under laser irradiation after intratumoral injection of such a kind of nanocomposites.

Key words: Fe3O4, gold shell, nanocomposites, photothermal therapy, MRI

中图分类号:

TQ174

翟云刚, 董文杰, 高勇平, 牛德超, 陈健壮, 顾金楼, 李永生, 施剑林. 超顺磁金纳米壳复合颗粒的粒径调控及其诊疗应用[J]. 无机材料学报, 2015, 30(9): 950-956.

ZHAI Yun-Gang, DONG Wen-Jie, GAO Yong-Ping, NIU De-Chao, CHEN Jian-Zhuang, GU Jin-Lou, LI Yong-Sheng, SHI Jian-Lin. Preparation of Superparamagnetic Gold Nanocomposites with Different Diameters and Their Imaging and Therapy Applications[J]. Journal of Inorganic Materials, 2015, 30(9): 950-956.

图/表 7

图1 SGNs不同制备阶段(a)以及不同粒径SGNs(b)的动态光散射粒径分布图

Fig. 1 Dynamic size distributions of the SGNs at different stages (a) and different diameters (b)

图2 不同粒径的Au-SSCNs和SGNs的SEM照片

Fig. 2 SEM images of Au-SSCNs and SGNs with different diameters (a) Au-SSCNs-1; (b) Au-SSCNs-2; (c) Au-SSCNs-3; (d) SGNs-1; (e) SGNs-2; (f) SGNs-3

图3 不同粒径的Au-SSCNs和SGNs的TEM照片

Fig. 3 TEM images of Au-SSCNs and SGNs with different diameters (a) Au-SSCNs-1; (b) Au-SSCNs-2; (c) Au-SSCNs-3; (d) SGNs-1; (e) SGNs-2; (f) SGNs-3

图4 不同粒径的SGNs 的紫外-可见光吸收图谱及其溶液光学照片(a)和经SH-PEG修饰后不同粒径的SGNs-PEG复合颗粒在808 nm激光照射下温度随时间变化规律图(b)

Fig. 4 UV-Vis spectra and digital photographs of SGNs with different diameters (a) and temperature change of SGNs-PEG with different diameters under irradiation time of 808 nm laser (b)

图5 不同粒径SGNs-PEG与MDA-MB-435细胞共培养后, 经808 nm激光照射的细胞成活率与金浓度的关系图(a)以及横向弛豫率(1/T2)随铁浓度变化的线性关系图(b)

Fig. 5 MDA-MB-435 cell viability cultured with SGNs-PEG at different Au concentrations under 808 nm laser irradiation (a) and plots of inverse transverse relaxation time (1/T2) vs Fe concentration (b)

图6 瘤内注射生理盐水和不同粒径SGNs-PEG的MDA-MB-435荷瘤小鼠在激光照射前后的热成像照片

Fig. 6 Infrared thermal images of saline and SGNs-PEG intratumoral injected tumor-bearing mices without (pre) and with (post) laser irradiation

图7 瘤内注射不同粒径SGNs-PEG前(pre)、后(post)荷瘤小鼠的磁共振成像图片

Fig. 7 In vivo T2-weighted MRIs of tumor-bearing mice before (pre) and after (post) intratumoral administration of SGNs-PEG of different diameters

参考文献 26

[1]	HUANG X H, EL-SAYED I H, QIAN W, et al. Cancer cells assemble and align gold nanorods conjugated to antibodies to produce highly enhanced, sharp, and polarized surface raman spectra: a potential cancer diagnostic marker.Nano Letters, 2007, 7(6): 1591-1597.
[2]	ROSI N L, GILJOHANN D A, MIRKIN C A, et al.Oligonucletide- modified gold nanoparticles for intracellular gene regulation.Science, 2006, 312(5776): 1027-1030.
[3]	FUJIMOTO J G, BREZINSKI M E, SWANSON E A, et al.Optical biopsy and imaging using optical coherence tomography.Nature Medicine, 1995, 1: 970-972.
[4]	JAIN P K, HUANG X H, EL-SAYED M A, et al. Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine.Accounts of Chemical Research, 2008, 41(12): 1578-1586.
[5]	ARTHUR L, ADEN M K.Scattering of electromagnetic waves from two concentric spheres.Journal of Applied Physics, 1951, 22(10): 1242-1246.
[6]	OLDENBURG S J, AVERITT R D, HALAS N J, et al.Nanoengineering of optical resonances.Chemical Physics Letters, 1998, 288(1): 243-247.
[7]	WEST J L, HALAS N J.Engineered nanomaterials for biophotonics applications: improving sensing, imaging, and therapeutics.Annual Review of Biomedical Engineering, 2003, 5(1): 285-292.
[8]	LOO C, LOWERY A, HALAS N J, et al.Immunotargeted nanoshells for integrated cancer imaging and therapy.Nano Letters, 2005, 5(4): 709-711.
[9]	O'NEAL D P, HIRSCH L R, HALAS N J, et al. Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles.Cancer letters, 2004, 209(2): 171-176.
[10]	HIRSCH L R, STAFFORD R J, WEST J L, et al.Nanoshell- mediated near-infrared thermal therapy of tumors under magnetic resonance guidance.Proceedings of the National Academy of Sciences, 2003, 100(23): 13549-13554.
[11]	BARHOUMI A, HUSCHKA R, HALAS N J, et al.Light-induced release of DNA from plasmon-resonant nanoparticles: towards light-controlled gene therapy.Chemical Physics Letters, 2009, 482(4): 171-179.
[12]	CHENG L, YANG K, LIU Z, et al.Facile preparation of multifunctional upconversion nanoprobes for multimodal imaging and dual-targeted photothermal therapy.Angewandte Chemie International Edition, 2011, 50(32): 7385-7390.
[13]	LIU H Y, LIU T L, TANG F Q, et al.Targeting gold nanoshells on silica nanorattles: a drug cocktail to fight breast tumors via a single irradiation with near-infrared laser light.Advanced Materials, 2012, 24(6): 755-761.
[14]	LIU H Y, CHEN D, TANG F Q, et al.Multifunctional gold nanoshells on silica nanorattles: a platform for the combination of photothermal therapy and chemotherapy with low systemic toxicity.Angewandte Chemie International Edition, 2011, 50(4): 891-895.
[15]	BARDHAN R, CHEN W, HALAS N J, et al.Nanoshells with targeted simultaneous enhancement of magnetic and optical imaging and photothermal therapeutic response.Advanced Functional Materials, 2009, 19(24): 3901-3909.
[16]	CHEN W, BARDHAN R, JOSHI A, et al.A molecularly targeted theranostic probe for ovarian cancer.Molecular Cancer Therapeutics, 2010, 9(4): 1028-1038.
[17]	PRIYAM A, IDRIS N M, ZHANG Y.Gold nanoshell coated NaYF4 nanoparticles for simultaneously enhanced upconversion fluorescence and dark-field imaging.Journal of Materials Chemistry, 2012, 22(3): 960-965.
[18]	KIM J, PARK S, HYEON T, et al.Designed fabrication of multifunctional magnetic gold nanoshells and their application to magnetic resonance imaging and photothermal therapy.Angewandte Chemie International Edition, 2006, 45(46): 7754-7758.
[19]	JI X, SHAO R, LI C, et al.Bifunctional gold nanoshells with a superparamagnetic iron oxide-silica core suitable for both MR imaging and photothermal therapy.The Journal of Physical Chemistry C, 2007, 111(17): 6245-6251.
[20]	NIU D C, LI Y S, SHI J L, et al.A facile approach to fabricate functionalized superparamagnetic copolymer-silica nanocomposite spheres.Chemical Communications, 2008, 37: 4463-4465.
[21]	DONG W J, LIY S, SHI J L, et al.Facile synthesis of monodisperse superparamagnetic Fe3O4 core@hybrid@Au shell nanocomposite for biomodal imaging and photothermal therapy.Advanced Materials, 2011, 23(45): 5392-5397.
[22]	SUN S H, ZENG H, ROBINSON D B, et al.Monodisperse MFe2O4 (M = Fe, Co, Mn) nanoparticles.Journal of the American Chemical Society, 2004, 126(1): 273-279.
[23]	DURAISWAMY S, KHAN S A.Plasmonic nanoshell synthesis in microfluidic composite foams.Nano Letters, 2010, 10(9): 3757-3763.
[24]	KE H T, WANG J R, LIU J B, et al.Gold-nanoshelled microcapsules: a theranostic agent for ultrasound contrast imaging and photothermal therapy. Angewandte Chemie International Edition, 2011, 50(13): 3017-3021.
[25]	PAQUET C, LEEK D M, SIMARD B, et al.Clusters of superparamagnetic iron oxide nanoparticles encapsulated in a hydrogel: a particle architecture generating a synergistic enhancement of the T2 relaxation.ACS Nano, 2011, 5(4): 3104-3112.
[26]	SPERLING R A, RIVERA G P, PARAK W J, et al.Biological applications of gold nanoparticles.Chemical Society Reviews, 2008, 37(9): 1896-1908.