Khan Memona, Boumati Sarah, Arib Celia, Thierno Diallo Amadou, Djaker Nadia, Doan Bich-Thuy, Spadavecchia Jolanda
CNRS, UMR 7244, CSPBAT, Laboratoire de Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques, Université Sorbonne Paris Nord, Bobigny, 93000, France.
CNRS UMR 8060, iCLeHS, Synthèse, Electrochimie, Imagerie et Systèmes Analytiques Pour le Diagnostic SEISAD, Chimie ParisTech, Université PSL, Paris, 75231, France.
Int J Nanomedicine. 2021 Mar 17;16:2219-2236. doi: 10.2147/IJN.S295809. eCollection 2021.
In this paper, we have designed and formulated, a novel synthesis of doxorubicin (DOX) loaded bimetallic gold nanorods in which gold salt (HAuCl) is chelated with anthracycline (DOX), diacid polyethylene-glycol (PEG-COOH) and gadolinium salt (GdCl * 6 HO) to form DOX IN-Gd-AuNRs compared with DOX ON-Gd-AuNRs in which the drug was grafted onto the bimetallic pegylated nanoparticle surface by electrostatic adsorption.
The physical and chemical evaluation was performed by spectroscopic analytical techniques (Raman spectroscopy, UV-Visible and transmission electron microscopy (TEM)). Magnetic features at 7T were also measured. Photothermal abilities were assessed. Cytotoxicity studies on MIA PaCa-2, human pancreatic carcinoma and TIB-75 hepatocytes cell lines were carried out to evaluate their biocompatibility and showed a 320 fold higher efficiency for DOX after encapsulation.
Exhaustive physicochemical characterization studies were conducted showing a mid size of 20 to 40 nm diameters obtained with low polydispersity, efficient synthesis using seed mediated synthesis with chelation reaction with high scale-up, long duration stability, specific doxorubicin release with acidic pH, strong photothermal abilities at 808 nm in the NIR transparency window, strong magnetic r relaxivities for positive MRI, well adapted for image guided therapy and therapeutical purpose in biological tissues.
In this paper, we have developed a novel theranostic nanoparticle composed of gadolinium complexes to gold ions, with a PEG biopolymer matrix conjugated with antitumoral doxorubicin, providing multifunctional therapeutic features. Particularly, these nano conjugates enhanced the cytotoxicity toward tumoral MIAPaCa-2 cells by a factor of 320 compared to doxorubicin alone. Moreover, MRI T features at 7T enables interesting positive contrast for bioimaging and their adapted size for potential passive targeting to tumors by Enhanced Permeability Retention. Given these encouraging antitumoral and imaging properties, this bimetallic theranostic nanomaterial system represents a veritable promise as a therapeutic entity in the field of medicinal applications.
在本文中，我们设计并制备了一种新型的负载阿霉素（DOX）的双金属金纳米棒，其中金盐（HAuCl）与蒽环类药物（DOX）、二酸聚乙二醇（PEG-COOH）和钆盐（GdCl·6H₂O）螯合形成DOX IN-Gd-AuNRs，与之相比，DOX ON-Gd-AuNRs是通过静电吸附将药物接枝到双金属聚乙二醇化纳米颗粒表面。
通过光谱分析技术（拉曼光谱、紫外可见光谱和透射电子显微镜（TEM））进行物理和化学评估。还测量了7T时的磁特性。评估了光热能力。对MIA PaCa-2、人胰腺癌和TIB-75肝细胞系进行细胞毒性研究，以评估它们的生物相容性，结果显示包封后阿霉素的效率提高了320倍。
进行了详尽的物理化学表征研究，结果表明其直径中等大小为20至40nm，多分散性低，通过种子介导合成与螯合反应进行高效合成，放大倍数高，稳定性持续时间长，在酸性pH下有特定的阿霉素释放，在近红外透明窗口的808nm处有强光热能力，对正性磁共振成像有强磁弛豫率，非常适合生物组织中的图像引导治疗和治疗目的。
在本文中，我们开发了一种新型的治疗诊断纳米颗粒，其由钆配合物与金离子组成，具有与抗肿瘤阿霉素共轭的聚乙二醇生物聚合物基质，提供多功能治疗特性。特别是，与单独的阿霉素相比，这些纳米缀合物对肿瘤MIAPaCa-2细胞的细胞毒性增强了320倍。此外，7T时的磁共振成像T特性为生物成像提供了有趣的正性对比，并且其合适的尺寸可通过增强的通透性滞留实现对肿瘤的潜在被动靶向。鉴于这些令人鼓舞的抗肿瘤和成像特性，这种双金属治疗诊断纳米材料系统在医学应用领域作为一种治疗实体具有真正的前景。
