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Synthesis and Biochemical Evaluation of Samarium-153 Oxide Nanoparticles Functionalized with iPSMA-Bombesin Heterodimeric Peptide.
Journal of Biomedical Nanotechnology Pub Date : 2020-9-14 , DOI: 10.1166/jbn.2020.2924
D. Trujillo-Benítez , G. Ferro-Flores , E. Morales-Avila , N. Jiménez-Mancilla , A. Ancira-Cortez , B. Ocampo-García , C. Santos-Cuevas , A. Escudero-Castellanos , M. Luna-Gutiérrez , E. Azorín-Vega

Developments in the design of lanthanide oxide nanoparticles (NPs) have unleashed a wide variety of biomedical applications. Several types of hepatic cancer cells overexpress two proteins: the gastrin-releasing peptide receptor (GRPr), which specifically recognizes the bombesin (BN) peptide, and the prostate-specific membrane antigen (PSMA), which specifically binds to several peptides that inhibit its activity (iPSMA). This research synthesized and physicochemically characterized Sm₂O₃ nanoparticles functionalized with the iPSMA-BN heterodimeric peptide and studied the effects on their structural, biochemical and preclinical properties after activation by neutron irradiation for possible use in molecular dual-targeted radiotherapy of hepatocellular carcinoma. The Sm₂O₃ NPs were synthesized by the precipitation-calcination method and functionalized with iPSMA-BN peptide using the DOTA macrocycle as a linking agent. Analysis of physicochemical characterization via TEM, EDS, XRD, UV-Vis, FT-IR, DSL, and zeta potential results showed the formation of Sm₂O₃-iPSMA-BN NPs (94.23 ± 5.98 nm), and their physicochemical properties were not affected after neutron activation. The nanosystem showed a high affinity with respect to PSMA and GRPr in HepG2 cells ( K d = 6.6 ± 1.6 nM) and GRPr in PC3 cells ( K d = 10.6 ± 1.9 nM). 153Sm₂O₃-iPSMA-BN NPs exhibited radioluminescent properties, making possible in vivo optical imaging of their biodistribution in mice. The results obtained from this research support further preclinical studies designed to evaluate the dosimetry and therapeutic efficacy of 153Sm₂O₃-iPSMA-BN nanoparticles for in vivo imaging and molecular dual-targeted radiotherapy of liver tumors overexpressing PSMA and/or GRPr proteins.

中文翻译:

iPSMA-Bombesin异二聚体肽功能化的153氧化mar纳米粒子的合成和生化评估。

镧系元素氧化物纳米颗粒(NPs)设计的发展已经释放了各种各样的生物医学应用。几种类型的肝癌细胞过表达两种蛋白质:特异性识别蛙皮素(BN)肽的胃泌素释放肽受体(GRPr),和特异性结合抑制它的几种肽的前列腺特异性膜抗原(PSMA)。活动(iPSMA)。这项研究合成了iPSMA-BN异二聚肽功能化的Sm 2 O 3纳米颗粒,并对其进行了物理化学表征,并研究了中子辐照活化后对其结构,生化和临床前性质的影响,以用于肝细胞癌的分子双靶放射治疗。Sm 2 O 3 NP通过沉淀-煅烧方法合成,并使用DOTA大环作为连接剂,用iPSMA-BN肽官能化。通过TEM,EDS,XRD,UV-Vis,FT-IR,DSL和zeta电势分析物化特性,结果表明Sm 2 O 3 -iPSMA-BN NPs的形成(94.23±5.98 nm),并且其理化性质在中子活化。纳米系统对HepG2细胞中的PSMA和GRPr具有很高的亲和力(K d = 6.6±1.6 nM)和PC3细胞中的GRPr(K d = 10.6±1.9 nM)。153个Sm 2 O 3 -iPSMA-BN NPs具有放射发光特性,使得它们在小鼠体内的生物分布体内光学成像成为可能。从这项研究中获得的结果支持了进一步的临床前研究,旨在评估153 Sm 2 O 3 -iPSMA-BN纳米粒子的剂量学和治疗效果,以对过表达PSMA和/或GRPr蛋白的肝肿瘤进行体内成像和分子双靶放射治疗。
更新日期:2020-09-16
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