金纳米颗粒生物探针的制备及其在生物医学中的应用
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摘要
近些年来,球形金纳米颗粒和金纳米棒以其独特的物理化学性质如在光学方面的局部表面等离子体共振的优越特性以及良好的生物相容性、简便有效的表面修饰等特性受到了人们广泛的关注,并使其在生物传感器、药物输送、肿瘤细胞的靶向诊断与治疗方面等领域都开展了广泛的研究与应用。
本文采用晶种生长法制备了阳离子表面活性剂十六烷基三甲基溴化胺(CTAB)保护的金纳米棒,并用带有负电荷的聚电解质聚丙烯酸(PAA)修饰其表面,通过静电吸引的方式用于承载具有正电荷的抗肿瘤药物阿霉素(DOX),从而得到了基于金纳米棒的药物载体。随后,我们研究了这种金纳米棒药物载体在前列腺癌DU145细胞治疗中的作用。此外,我们又提出了一种新的合成方法,利用半乳糖胺(D-galactosamine)一步还原氯金酸(HAuCl4),得到了能主动靶向识别肝癌细胞的新型金纳米颗粒探针。制备方法简单易行,产物尺寸均一、单分散性好,通过调节溶液的pH值就可以控制金颗粒的尺寸。在此基础上,我们又成功的将这种半乳糖保护的金纳米颗粒探针用于检测蓖麻凝集素RCA120 ,此方法的检测限达到2 ng/mL。本文所用的表征方法主要包括透射电子显微镜、荧光显微镜、紫外可见分光光度计和荧光分光光度计等。
In recent years, spherical gold nanoparticles (GNPs) and gold nanorods (GNRs) have gained increasing interest owing to their unique physical and chemical properties, such as excellent optical property in localized surface plasmon resonance (LSPR), good biocompatibility, easy and efficient surface modification. Many applications in various fields in biosensing, drug delivery and site-specific diagnostic and therapy in cancer have been developed.
Herein, water-soluble GNRs were synthesized via a well-established seed-mediated method, using the cationic surfactant cetyltrimethylammonium bromide (CTAB) as a capping agent. To employ as a carrier for drug delivery, the surfaces of GNRs were modified with thioled poly(ethylene glycol) SH-PEG and negatively charged polyelectrolyte polyacrylic acid (PAA) to get the stable GNRs probes in different solutions with negative charged surfaces. Then positively charged anti-cancer drug, doxorubicin, was loaded onto the surfaces of GNRs via electrostatic attraction. Drug-loaded PEG-PAA-GNRs probes was carried out for the treatment of prostate cancer DU145 cells, demonstrating that the GNRs probes can serves as a promising carrier for drug delivery. In addition, we developed a novel one-pot method to fabricate monodispersed GNPs by reducing HAuCl4 with galactosamine. The method was easy to operate and the size of GNRs can be simply controlled by changing the pH of solution. Furthermore, the as-prepared GNPs were successfully utilized as a novel bioprobe for the rapid and sensitive detection of ricin agglutinin RCA120 with the detection limit of 2 ng/mL. The characterization method used here are transmission electron microscopy (TEM), fluorescence spectrophotometer, fluorescence microscopy, UV-Vis spectrophotometer, and etc.
本文采用晶种生长法制备了阳离子表面活性剂十六烷基三甲基溴化胺(CTAB)保护的金纳米棒,并用带有负电荷的聚电解质聚丙烯酸(PAA)修饰其表面,通过静电吸引的方式用于承载具有正电荷的抗肿瘤药物阿霉素(DOX),从而得到了基于金纳米棒的药物载体。随后,我们研究了这种金纳米棒药物载体在前列腺癌DU145细胞治疗中的作用。此外,我们又提出了一种新的合成方法,利用半乳糖胺(D-galactosamine)一步还原氯金酸(HAuCl4),得到了能主动靶向识别肝癌细胞的新型金纳米颗粒探针。制备方法简单易行,产物尺寸均一、单分散性好,通过调节溶液的pH值就可以控制金颗粒的尺寸。在此基础上,我们又成功的将这种半乳糖保护的金纳米颗粒探针用于检测蓖麻凝集素RCA120 ,此方法的检测限达到2 ng/mL。本文所用的表征方法主要包括透射电子显微镜、荧光显微镜、紫外可见分光光度计和荧光分光光度计等。
In recent years, spherical gold nanoparticles (GNPs) and gold nanorods (GNRs) have gained increasing interest owing to their unique physical and chemical properties, such as excellent optical property in localized surface plasmon resonance (LSPR), good biocompatibility, easy and efficient surface modification. Many applications in various fields in biosensing, drug delivery and site-specific diagnostic and therapy in cancer have been developed.
Herein, water-soluble GNRs were synthesized via a well-established seed-mediated method, using the cationic surfactant cetyltrimethylammonium bromide (CTAB) as a capping agent. To employ as a carrier for drug delivery, the surfaces of GNRs were modified with thioled poly(ethylene glycol) SH-PEG and negatively charged polyelectrolyte polyacrylic acid (PAA) to get the stable GNRs probes in different solutions with negative charged surfaces. Then positively charged anti-cancer drug, doxorubicin, was loaded onto the surfaces of GNRs via electrostatic attraction. Drug-loaded PEG-PAA-GNRs probes was carried out for the treatment of prostate cancer DU145 cells, demonstrating that the GNRs probes can serves as a promising carrier for drug delivery. In addition, we developed a novel one-pot method to fabricate monodispersed GNPs by reducing HAuCl4 with galactosamine. The method was easy to operate and the size of GNRs can be simply controlled by changing the pH of solution. Furthermore, the as-prepared GNPs were successfully utilized as a novel bioprobe for the rapid and sensitive detection of ricin agglutinin RCA120 with the detection limit of 2 ng/mL. The characterization method used here are transmission electron microscopy (TEM), fluorescence spectrophotometer, fluorescence microscopy, UV-Vis spectrophotometer, and etc.
引文
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