Soft Condensed Matter Lab , Raman Research Institute , Bangalore 560080 , India.
ACS Appl Mater Interfaces. 2018 Apr 18;10(15):12960-12974. doi: 10.1021/acsami.7b19109. Epub 2018 Apr 4.
The prospective design of nanocarriers for personalized oncotherapy should be an ensemble of targeting, imaging, and noninvasive therapeutic capabilities. Herein, we report the development of the inverse hexagonal nano-liquid crystalline (NLC) particles that are able to host formononetin (FMN), a phytoestrogen with known anticancer activity, and tetraphenylethene (TPE), an iconic optical beacon with aggregation-induced emission (AIE) signature, simultaneously. Ordered three-dimensional mesoporous internal structure and high-lipid-volume fraction of NLC nanoparticles (NLC NPs) frame the outer compartment for the better settlement of payloads. Embellishment of these nanoparticles by anisamide (AA), a novel sigma receptor targeting ligand using carbodiimide coupling chemistry ensured NLC's as an outstanding vehicle for possible utility in surveillance of tumor location as well as the FMN delivery through active AIE imaging. The size and structural integrity of nanoparticles were evaluated by quasi-elastic light scattering, cryo field emission scanning electron microscopy small-angle X-ray scattering. The existence of AIE effect in the nanoparticles was evidenced through the photophysical studies that advocate the application of NLC NPs in fluorescence-based bioimaging. Moreover, confocal microscopy illustrated the single living cell imaging ability endowed by the NLC NPs. In vitro and in vivo studies supported the enhanced efficacy of targeted nanoparticles (AA-NLC-TF) in comparison to nontargeted nanoparticles (NLC-TF) and free drug. Apparently, this critically designed multimodal NLC NPs may establish a promising platform for targeted and image-guided chemotherapy for breast cancer.
用于个性化肿瘤治疗的纳米载体的前瞻性设计应该是靶向、成像和非侵入性治疗能力的综合。在此,我们报告了能够同时容纳芒柄花素(FMN)和四苯乙烯(TPE)的反向六方纳米液晶(NLC)粒子的开发,FMN 是一种具有已知抗癌活性的植物雌激素,TPE 是一种具有聚集诱导发射(AIE)特征的标志性光学信标。有序的三维介孔内部结构和 NLC 纳米粒子(NLC NPs)的高脂质体积分数构成了外部隔室,以便更好地容纳有效载荷。通过碳二亚胺偶联化学修饰异酰胺(AA),一种新型的 sigma 受体靶向配体,对这些纳米粒子进行修饰,确保 NLC 作为一种出色的载体,可用于监测肿瘤位置,以及通过主动 AIE 成像递送 FMN。通过准弹性光散射、低温场发射扫描电子显微镜小角 X 射线散射评估了纳米粒子的尺寸和结构完整性。通过光物理研究证明了纳米粒子中存在 AIE 效应,这表明 NLC NPs 可应用于荧光基生物成像。此外,共聚焦显微镜说明了 NLC NPs 赋予的单个活细胞成像能力。体外和体内研究支持靶向纳米粒子(AA-NLC-TF)与非靶向纳米粒子(NLC-TF)和游离药物相比,具有增强的疗效。显然,这种精心设计的多模式 NLC NPs 可能为乳腺癌的靶向和图像引导化疗建立一个有前途的平台。