Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.
Department of Radiology, Duke University Medical Center, Durham, NC, 27710, USA.
Int J Nanomedicine. 2021 Oct 28;16:7297-7305. doi: 10.2147/IJN.S327577. eCollection 2021.
To develop an innovative At nanoplatform with high radiolabeling efficiency and low in vivo deastatination for future targeted alpha-particle therapy (TAT) to treat cancer.
Star-shaped gold nanoparticles, gold nanostars (GNS), were used as the platform for At radiolabeling. Radiolabeling efficiency under different reaction conditions was tested. Uptake in the thyroid and stomach after systemic administration was used to evaluate the in vivo stability of At-labeled GNS. A subcutaneous U87MG human glioma xenograft murine model was used to preliminarily evaluate the therapeutic efficacy of At-labeled GNS after intratumoral administration.
The efficiency of labeling GNS with At was almost 100% using a simple and rapid synthesis process that was completed in only 1 min. In vitro stability test in serum showed that more than 99% of the At activity remained on the GNS after 24 h incubation at 37°C. In vivo biodistribution results showed low uptake in the thyroid (0.44-0.64%ID) and stomach (0.21-0.49%ID) between 0.5 and 21 h after intravenous injection, thus indicating excellent in vivo stability of At-labeled GNS. The preliminary therapeutic efficacy study demonstrated that At labeled GNS substantially reduced tumor growth (P < 0.001; two-way ANOVA) after intratumoral administration.
The new At radiolabeling strategy based on GNS has the advantages of a simple process, high labeling efficiency, and minimal in vivo dissociation, making it an attractive potential platform for developing TAT agents that warrants further evaluation in future preclinical studies directed to evaluating prospects for clinical translation.
开发一种具有高效放射性标记和低体内脱靶特性的新型金纳米星（GNS）载钅艾平台，用于未来的靶向α粒子治疗（TAT）癌症治疗。
以星型金纳米粒子（GNS）作为载钅艾平台，测试不同反应条件下的放射性标记效率。通过系统给药后甲状腺和胃的摄取来评估放射性标记 GNS 的体内稳定性。采用皮下 U87MG 人胶质母细胞瘤异种移植鼠模型，初步评价瘤内注射放射性标记 GNS 的治疗效果。
采用简单快速的合成工艺，1 分钟内即可完成，GNS 的放射性标记效率几乎达到 100%。在 37°C 孵育 24 小时的血清体外稳定性试验中，超过 99%的放射性标记 GNS 活性仍保持稳定。体内生物分布结果显示，静脉注射后 0.5 至 21 小时，甲状腺（0.44-0.64%ID）和胃（0.21-0.49%ID）摄取率较低，表明放射性标记 GNS 具有良好的体内稳定性。初步治疗效果研究表明，瘤内注射放射性标记 GNS 可显著降低肿瘤生长（P<0.001；双向方差分析）。
基于 GNS 的新型放射性标记策略具有工艺简单、标记效率高、体内解离少的优点，是开发 TAT 药物的有吸引力的潜在平台，值得进一步在未来的临床前研究中评估，以评估其临床转化前景。
