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Dy₂O₃/Ho₂O₃-iPSMA 纳米颗粒的制备及其用于肝癌靶向放疗的剂量评估。

Preparation and Dosimetry Assessment of Dy₂O₃/Ho₂O₃-iPSMA Nanoparticles for Targeted Hepatocarcinoma Radiotherapy.

机构信息

Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico.

Cátedras CONACyT Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico.

出版信息

J Nanosci Nanotechnol. 2021 Nov 1;21(11):5449-5458. doi: 10.1166/jnn.2021.19455.

Abstract

This research aimed to prepare Dy₂O₃-iPSMA/Ho₂O₃-iPSMA nanoparticles (Dy₂O₃/Ho₂O₃-iPSMA NPs) and assess the radiation absorbed dose produced by the nanosystem to hepatic cancer cells by using experimental and biokinetic data. Dy₂O₃NPs were synthesized and functionalized with the prostate-specific membrane antigen inhibitor peptide (iPSMA). Fourier transform infrared (FTIR) spectroscopy, transmission electron microscope (TEM), dynamic light scattering (DSL) and zeta potential analyses indicated the formation of Dy₂O₃-iPSMA NPs (46.11 ± 13.24 nm). After neutron activation, a stable Dy₂O₃/Ho₂O₃- iPSMA nanosystem was obtained, which showed adequate affinity to the PSMA receptor in HepG2 cancer cells (K = 9.87 ± 2.27 nM). studies indicated high Dy₂O₃/Ho₂O₃-iPSMA internalization in cancer cells, with high radiation doses to cell nuclei (107 Gy) and cytotoxic effects, resulting in a significant reduction in HepG2 cell viability (decreasing to 2.12 ± 0.31%). After intratumoral administration in mice, the nanosystem biokinetic profile indicated significant retention into the tumoral mass, producing ablative radiation doses (>70 Gy).

摘要

本研究旨在制备 Dy₂O₃-iPSMA/Ho₂O₃-iPSMA 纳米粒子(Dy₂O₃/Ho₂O₃-iPSMA NPs),并利用实验和生物动力学数据评估纳米系统对肝癌细胞产生的辐射吸收剂量。合成了 Dy₂O₃NPs 并对其进行了前列腺特异性膜抗原抑制剂肽(iPSMA)的功能化。傅里叶变换红外(FTIR)光谱、透射电子显微镜(TEM)、动态光散射(DSL)和zeta 电位分析表明形成了 Dy₂O₃-iPSMA NPs(46.11±13.24nm)。经过中子激活,获得了稳定的 Dy₂O₃/Ho₂O₃-iPSMA 纳米系统,该系统对 HepG2 癌细胞中的 PSMA 受体具有足够的亲和力(K=9.87±2.27nM)。研究表明,Dy₂O₃/Ho₂O₃-iPSMA 在癌细胞内有很高的内化作用,对细胞核有很高的辐射剂量(107Gy)和细胞毒性作用,导致 HepG2 细胞活力显著降低(降至 2.12±0.31%)。在小鼠肿瘤内给药后,纳米系统的生物动力学特征表明其在肿瘤组织中有明显的滞留,产生了消融性辐射剂量(>70Gy)。

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