Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB).

Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB).
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免疫原性智能放射治疗生物材料(iSRB)药效学的临床前研究。

DOI:
10.3390/pharmaceutics15122778
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发表时间:
2023-12-14
期刊:
影响因子:
5.4
通讯作者:
Yasmin-Karim S
Yasmin-Karim S
中科院分区:
医学2区
文献类型:
--
作者:
Moreau M;Acter S;Ngema LM;Bih N;Sy G;Keno LS;Chow KF;Sajo E;Nebangwa O;Walker J;Oh P;Broyles E;Ngwa W;Yasmin-Karim S

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使用免疫原性的SMART放射治疗生物材料(ISRB)运送抗CD40在动物模型中治疗不同的癌症是有效的。这项研究进一步表征了使用iSRB来评估健康C57BL6小鼠的任何相关毒性。将聚乳酸-乙醇酸(PLGA)聚合物与二氧化钛(TiO2)纳米颗粒混合在其基质中,制备了iSRB。动物研究包括自由注射抗CD40、抗CD40负载的iSRB、卸载的iSRB和对照(健康)动物队列。在治疗后的预定时间点处死小鼠,以评估与肾和肝脏毒性有关的血清化学和细胞计数参数,以及感兴趣器官的病理报告。结果显示,在所有队列中,肝和肾功能相似。结果表明,与健康的未经治疗的动物相比,使用带有或不带有抗CD40抗体的iSRB没有任何明显的毒性。这些发现为进一步研究iSRB的治疗效果和安全性以及进一步的临床翻译工作提供了有用的参考。
The use of an immunogenic smart radiotherapy biomaterial (iSRB) for the delivery of anti-CD40 is effective in treating different cancers in animal models. This study further characterizes the use of iSRBs to evaluate any associated toxicity in healthy C57BL6 mice. iSRBs were fabricated using a poly-lactic-co-glycolic-acid (PLGA) polymer mixed with titanium dioxide (TiO2) nanoparticles incorporated into its matrix. Animal studies included investigations of freely injected anti-CD40, anti-CD40-loaded iSRBs, unloaded iSRBs and control (healthy) animal cohorts. Mice were euthanized at pre-determined time points post-treatment to evaluate the serum chemistry pertaining to kidney and liver toxicity and cell blood count parameters, as well as pathology reports on organs of interest. Results showed comparable liver and kidney function in all cohorts. The results indicate that using iSRBs with or without anti-CD40 does not result in any significant toxicity compared to healthy untreated animals. The findings provide a useful reference for further studies aimed at optimizing the therapeutic efficacy and safety of iSRBs and further clinical translation work.
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