Shestovskaya Maria V, Luss Anna L, Bezborodova Olga A, Venidiktova Yulia B, Vorontsova Maria S, Vlaskina Elizaveta R, Kushnerev Kirill K, Kulikov Pavel P, Makarov Valentin V, Yudin Vladimir S, Keskinov Anton A
Federal State Budgetary Institution "Centre for Strategic Planning and Management of Biomedical Health Risks" of the Federal Medical Biological Agency, Schukinskaya st. 5/1, Moscow 119435, Russia.
P. Hertsen Moscow Oncology Research Institute - Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation; Second Botkinskiy p. 3, Moscow 125284, Russia.
ACS Appl Bio Mater. 2025 Mar 17;8(3):2535-2547. doi: 10.1021/acsabm.4c01978. Epub 2025 Mar 4.
This research aimed to evaluate the potency of preparation based on heparinized iron oxide nanoparticles (hIONPs) in combination with radiation therapy, including magnetic delivery via the applied magnetic field (AMF), in sarcoma and cervical cancer models. For in vitro studies, cells of rhabdomyosarcoma (RD), fibrosarcoma (HT1080), and cervical cancer (HeLa S3) were treated with hIONPs and analyzed for survival rate and hIONP uptake. Then, cell morphology, cell cycle, increase of reactive oxygen species, mitochondria depolarization, and ability to form colonies were assessed for combined treatment (hIONPs + 3Gy). For in vivo research, hIONPs were administered once in the hybrids of CBAxC57Bl/6j mice, grafted with sarcoma (S37) and cervical cancer (CC5) strains. The ultimate in vivo treatment modes were: (1) i.v. hIONPs (14 μg/kg) + 5 Gy; (2) i.v. hIONPs (14 μg/kg) + AMF + 5 Gy; and (3) i.t. hIONPs (2,8 μg/kg) + 5 Gy. The overall survival rates, increase in life expectancy, inhibition of tumor growth (tumor growth inhibition), and degree of inhibition (T/C) were determined, and pathomorphological changes were assessed in experimental groups. The combined treatment in vitro (hIONPs + 3Gy) promotes multiple tumor cell death with high-severity peroxide effects compared with other groups. The sarcoma cells were more sensitive than cervical cancer cells. For in vivo, an enhancing effect was revealed by the combination of radiotherapy and magnetic-delivered hIONPs. For S37 tumor, the treatment regimen was characterized as having a high antitumor effect, ≪++++ ≫, with a 20% cure rate of mice. For the CC5 tumor, the effect was accompanied by the inhibition of tumor growth, an increase in the life expectancy of animals, and was characterized as a significant antitumor effect, ≪+++/++ ≫. From the data obtained, it can be concluded that the radiosensitizing potential of hIONPs may be taken as a basis of combined radiation treatment protocols.
本研究旨在评估基于肝素化氧化铁纳米颗粒（hIONPs）并结合放射治疗（包括通过外加磁场（AMF）进行磁性递送）在肉瘤和宫颈癌模型中的效力。对于体外研究，用hIONPs处理横纹肌肉瘤（RD）、纤维肉瘤（HT1080）和宫颈癌（HeLa S3）细胞，并分析其存活率和hIONP摄取情况。然后，评估联合治疗（hIONPs + 3Gy）后的细胞形态、细胞周期、活性氧增加、线粒体去极化以及形成集落的能力。对于体内研究，将hIONPs一次性给予接种了肉瘤（S37）和宫颈癌（CC5）菌株的CBAxC57Bl/6j小鼠杂交种。最终的体内治疗模式为：（1）静脉注射hIONPs（14μg/kg）+ 5Gy；（2）静脉注射hIONPs（14μg/kg）+ AMF + 5Gy；（3）瘤内注射hIONPs（2.8μg/kg）+ 5Gy。测定总体存活率、预期寿命增加、肿瘤生长抑制（肿瘤生长抑制）以及抑制程度（T/C），并评估实验组的病理形态学变化。与其他组相比，体外联合治疗（hIONPs + 3Gy）以高严重程度的过氧化物效应促进多种肿瘤细胞死亡。肉瘤细胞比宫颈癌细胞更敏感。在体内，放疗与磁性递送的hIONPs联合显示出增强作用。对于S37肿瘤，治疗方案具有高抗肿瘤效果，≪++++ ≫，小鼠治愈率为20%。对于CC5肿瘤，该效应伴随着肿瘤生长抑制、动物预期寿命增加，并且具有显著抗肿瘤效果≪+++/++ ≫。从获得的数据可以得出结论，hIONPs的放射增敏潜力可作为联合放射治疗方案的基础。
