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基于聚多巴胺的负载替莫唑胺纳米颗粒,通过肽-1缀合用于胶质母细胞瘤的化疗和光热治疗。

Polydopamine-based loaded temozolomide nanoparticles conjugated by peptide-1 for glioblastoma chemotherapy and photothermal therapy.

作者信息

Wu Hao, Zhang Tianyi, Liu Qi, Wei Min, Li Yuping, Ma Qiang, Wang Lianhui, Zhu Yufu, Zhang Hengzhu

机构信息

Graduate School of Dalian Medical University, Dalian, China.

Department of Neurosurgery, Clinical Medical College, Yangzhou University, Yangzhou, China.

出版信息

Front Pharmacol. 2023 Jan 18;14:1081612. doi: 10.3389/fphar.2023.1081612. eCollection 2023.

Abstract

Nanoparticles (NPs) of the polydopamine (PDA)-based,loaded with temozolomide (TMZ) and conjugated with Pep-1 (Peptide-1) as a feasible nano-drug delivery system were constructed and utilized for chemotherapy (CT) and photothermal therapy (PTT) of glioblastoma (GBM). PDA NPs were synthesized from dopamine (DA) hydrochloride and reacted with TMZ to obtain the PDA-TMZ NPs and then the PDA NPs and the PDA-TMZ NPs were conjugated and modified by Pep-1 to obtain the Pep-1@PDA NPs and Pep-1@PDA-TMZ NPs the Schiff base reaction (SBR), respectively.Their dimensions, charge, and shape were characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The assembly of TMZ was verified by Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet and visible spectroscopy (UV-Vis). The biostability of both the nanocarrier and the synthetic NPs were validated using water and fetal bovine serum (FBS). The antitumor activities of the PDA-TMZ NPs and Pep-1@PDA-TMZ NPs were verified in U87 cells and tumor-bearing nude mice. The prepared PDA NPs, PDA-TMZ NPs, Pep-1@PDA NPs, and Pep-1@PDA-TMZ NPs were regular and spherical, with dimension of approximately 122, 131, 136, and 140 nm, respectively. The synthetic nanoparticles possessed good dispersity, stability,solubility, and biocompatibility. No obvious toxic side effects were observed, and the loading rate of TMZ was approximately 50%. research indicated that the inhibition ratio of the Pep-1@PDA-TMZ NPs combined with 808 nm laser was approximately 94% for U87 cells and research was approximately 77.13%, which was higher than the ratio of the other groups ( < 0.05). Pep-1 was conjugated and modified to PDA-TMZ NPs, which can serve as a new targeted drug nano-delivery system and can offer a CT and PTT integration therapy against GBM. Thus, Pep-1@PDA-TMZ NPs could be a feasible approach for efficient GBM therapy, and further provide some evidence and data for clinical transformation so that gradually conquer GBM.

摘要

构建了一种基于聚多巴胺(PDA)、负载替莫唑胺(TMZ)并与Pep - 1(肽 - 1)偶联的纳米颗粒(NPs),作为一种可行的纳米药物递送系统,用于胶质母细胞瘤(GBM)的化疗(CT)和光热疗法(PTT)。由盐酸多巴胺(DA)合成PDA NPs,并使其与TMZ反应得到PDA - TMZ NPs,然后分别通过席夫碱反应(SBR)将PDA NPs和PDA - TMZ NPs与Pep - 1偶联和修饰,得到Pep - 1@PDA NPs和Pep - 1@PDA - TMZ NPs。通过动态光散射(DLS)和扫描电子显微镜(SEM)对其尺寸、电荷和形状进行表征。通过傅里叶变换红外光谱(FT - IR)和紫外可见光谱(UV - Vis)验证TMZ的组装情况。使用水和胎牛血清(FBS)验证纳米载体和合成NPs的生物稳定性。在U87细胞和荷瘤裸鼠中验证PDA - TMZ NPs和Pep - 1@PDA - TMZ NPs的抗肿瘤活性。制备的PDA NPs、PDA - TMZ NPs、Pep - 1@PDA NPs和Pep - 1@PDA - TMZ NPs呈规则球形,尺寸分别约为122、131、136和140 nm。合成的纳米颗粒具有良好的分散性、稳定性、溶解性和生物相容性。未观察到明显的毒副作用,TMZ的负载率约为50%。研究表明,Pep - 1@PDA - TMZ NPs与808 nm激光联合使用时,对U87细胞的抑制率约为94%,对肿瘤的抑制率约为77.13%,高于其他组(P < 0.05)。Pep - 1偶联修饰到PDA - TMZ NPs上,可作为一种新型靶向药物纳米递送系统,为GBM提供CT和PTT一体化治疗。因此,Pep - 1@PDA - TMZ NPs可能是一种有效的GBM治疗方法,并为临床转化提供一些证据和数据,从而逐步攻克GBM。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fad/9889548/725d94757437/fphar-14-1081612-g001.jpg

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