This study reports the in vivo performance of two tribenzyltin carboxylate complexes, tri(4-fluorobenzyl)tin[(N,N-diisopropylcarbamothioyl)sulfanyl]acetate (C1) and tribenzyltin isonicotinate (C9), in their native form as well as in a poly(lactic-co-glycolic acid) (PLGA)-based nanoformulation, to assess their potential to be translated into clinically useful agents. In a 4T1 murine metastatic mammary tumour model, single intravenous administration of C1 (2.7 mg/kg) and C9 (2.1 mg/kg; 2.1 mg/kg C9 is equivalent to 2.7 mg/kg C1) induced greater tumour growth delay than cisplatin and doxorubicin at equivalent doses, while a double-dose regimen demonstrated a much greater tumour growth delay than the single-dose treated groups. To improve the efficacy of the complexes in vivo, C1 and C9 were further integrated into PLGA nanoparticles to yield nanosized PLGA-C1 (183.7 ± 0.8 nm) and PLGA-C9 (163.2 ± 1.2 nm), respectively. Single intravenous administration of PLGA-C1 (2.7 mg C1 equivalent/kg) and PLGA-C9 (2.1 mg C9 equivalent/kg) induced greater tumour growth delay (33% reduction in the area under curve compared to that of free C1 and C9). Multiple-dose administration of PLGA-C1 (5.4 mg C1 equivalent/kg) and PLGA-C9 (4.2 mg C9 equivalent/kg) induced tumour growth suppression at the end of the study (21.7 and 34.6% reduction relative to the size on day 1 for the double-dose regimen; 73.5 and 79.0% reduction relative to the size on day 1 for the triple-dose regimen, respectively). Such tumour growth suppression was not observed in mice receiving multiple-dose regimens of free C1 and C9. Histopathological analysis revealed that metastasis to the lung and liver was inhibited in mice receiving PLGA-C1 and PLGA-C9. The current study has demonstrated the improved in vivo antitumour efficacies of C1 and C9 compared with conventional chemotherapy drugs and the enhancement of the efficacies of these agents via a robust PLGA-based nanoformulation and multiple-drug administration approach.

中文翻译：

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三苄基锡羧酸盐在 4T1 鼠转移性乳腺肿瘤模型中的体内抗肿瘤特性：PLGA 纳米颗粒增强疗效。

本研究报告了两种三苄基锡羧酸盐复合物，即三(4-氟苄基)锡[(N,N-二异丙基氨基甲硫基)硫烷基]乙酸酯 (C1) 和异烟酸三苄基锡 (C9) 的体内性能，它们的天然形式以及在基于聚（乳酸-共-乙醇酸）（PLGA）的纳米制剂，以评估其转化为临床有用药物的潜力。在 4T1 鼠转移性乳腺肿瘤模型中，单次静脉内给药 C1 (2.7 mg/kg) 和 C9 (2.1 mg/kg；2.1 mg/kg C9 相当于 2.7 mg/kg C1) 比顺铂和等剂量的阿霉素，而双剂量方案显示出比单剂量治疗组更大的肿瘤生长延迟。为了提高复合物在体内的功效，C1 和 C9 进一步整合到 PLGA 纳米颗粒中，分别产生纳米级 PLGA-C1 (183.7 ± 0.8 nm) 和 PLGA-C9 (163.2 ± 1.2 nm)。PLGA-C1（2.7 mg C1当量/kg）和PLGA-C9（2.1 mg C9当量/kg）单次静脉内给药诱导更大的肿瘤生长延迟（与游离C1和C9相比，曲线下面积减少33%） . PLGA-C1（5.4 mg C1 当量/kg）和 PLGA-C9（4.2 mg C9 当量/kg）的多剂量给药在研究结束时诱导肿瘤生长抑制（相对于当天的大小减少 21.7% 和 34.6%双剂量方案为 1；相对于三剂量方案第 1 天的大小分别减少 73.5% 和 79.0%）。在接受多剂量游离 C1 和 C9 方案的小鼠中未观察到这种肿瘤生长抑制。组织病理学分析显示，接受 PLGA-C1 和 PLGA-C9 的小鼠肺和肝脏的转移受到抑制。目前的研究表明，与传统化疗药物相比，C1 和 C9 的体内抗肿瘤功效有所提高，并且通过稳健的基于 PLGA 的纳米制剂和多种药物给药方法增强了这些药物的功效。