State Key Laboratory of Molecular Engineering of Polymers, State Key Laboratory of ASIC & System, Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University , 220 Handan Road, Shanghai 200433, People's Republic of China.
ACS Appl Mater Interfaces. 2017 Oct 18;9(41):35604-35612. doi: 10.1021/acsami.7b11392. Epub 2017 Oct 9.
The development of multifunctional ultrasound contrast agents has inspired considerable interest in the application of biomedical imaging and anticancer therapeutics. However, combining multiple components that can preferentially accumulate in tumors in a nanometer scale poses one of the major challenges in targeting drug delivery for theranostic application. Herein, reflux-precipitation polymerization, and N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide-meditated amidation reaction were introduced to effectively generate a new type of soft glycine/poly(ethylene glycol) (PEG)/RGD-modified poly(methacrylic acid) nanobubbles with a uniform morphology and desired particle size (less than 100 nm). Because of the enhanced biocompatibility resulting from the glycine modification, over 80% of the cells survived, even though the dosage of glycine-modified polymeric nanobubbles was up to 5 mg/mL. By loading doxorubicin as an anticancer drug and perfluorohexane as an ultrasound probe, the resulting glycine/PEG/RGD-modified nanobubbles showed remarkable cancer therapeutic efficacy and a high quality of ultrasonic imaging; thus, the ultrasonic signal exhibited a 1.47-fold enhancement at the tumor site after intravenous injection. By integrating diagnostic and therapeutic functions into a single nanobubble, the new type of theranostic nanobubbles offers a promising strategy to monitor the therapeutic effects, giving important insights into the ultrasound-traced and enhanced targeting drug delivery in biomedical applications.
多功能超声造影剂的发展激发了人们对生物医学成像和抗癌治疗应用的极大兴趣。然而，将能够优先在纳米尺度积聚在肿瘤中的多种成分结合在一起，是靶向药物输送用于治疗应用的主要挑战之一。在此，采用回流沉淀聚合和 N-(3-(二甲基氨基)丙基)-N'-乙基碳二亚胺介导的酰胺化反应，有效地生成了一种新型的软甘氨酸/聚乙二醇（PEG）/RGD 修饰的聚（甲基丙烯酸）纳米气泡，具有均匀的形态和所需的粒径（小于 100nm）。由于甘氨酸修饰提高了生物相容性，即使甘氨酸修饰的聚合物纳米气泡的剂量高达 5mg/mL，仍有超过 80%的细胞存活。通过装载阿霉素作为抗癌药物和全氟己烷作为超声探针，所得的甘氨酸/PEG/RGD 修饰纳米气泡显示出显著的癌症治疗效果和高质量的超声成像；因此，静脉注射后肿瘤部位的超声信号增强了 1.47 倍。通过将诊断和治疗功能集成到单个纳米气泡中，新型治疗诊断纳米气泡为监测治疗效果提供了一种很有前途的策略，为生物医学应用中的超声跟踪和增强靶向药物输送提供了重要的见解。
