Photothermal therapy co-localized with CD137 agonism improves survival in an SM1 melanoma model without hepatotoxicity.

Nanomedicine (London, England) Pub Date : 2024-01-01 Epub Date: 2024-09-03 DOI:10.1080/17435889.2024.2389770
Jacob A Medina, Debbie K Ledezma, Joshua Ghofrani, Jie Chen, Samantha J Chin, Preethi Bala Balakrishnan, Norman H Lee, Elizabeth E Sweeney, Rohan Fernandes
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Abstract

Aim: We investigate combining Prussian Blue nanoparticles (PBNPs), as photothermal therapy (PTT) agents, with agonistic CD137 antibodies (αCD137) on a single nanoparticle platform to deliver non-toxic, anti-tumor efficacy in SM1 murine melanoma.Methods: We electrostatically coated PBNPs with αCD137 (αCD137-PBNPs) and quantified their physicochemical characteristics, photothermal and co-stimulatory capabilities. Next, we tested the efficacy and hepatotoxicity of PTT using αCD137-PBNPs (αCD137-PBNP-PTT) in SM1 tumor-bearing mice.Results: The αCD137-PBNPs retained both the photothermal and agonistic properties of the PBNPs and αCD137, respectively. In vivo, SM1 tumor-bearing mice treated with αCD137-PBNP-PTT exhibited a significantly higher survival rate (50%) without hepatotoxicity, compared with control treatments.Conclusion: These data suggest the potential utility of co-localizing PBNP-PTT with αCD137-based agonism as a novel combination nanomedicine.

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光热疗法与CD137激动剂共定位可提高SM1黑色素瘤模型的存活率,且无肝毒性。
目的:我们研究了在单一纳米粒子平台上将普鲁士蓝纳米粒子(PBNPs)作为光热疗法(PTT)制剂与激动剂CD137抗体(αCD137)相结合,以在SM1小鼠黑色素瘤中发挥无毒的抗肿瘤疗效:我们在 PBNPs 上静电包覆了 αCD137 (αCD137-PBNPs),并对其理化特性、光热和协同刺激能力进行了量化。接着,我们使用αCD137-PBNPs(αCD137-PBNP-PTT)在SM1肿瘤小鼠中测试了PTT的疗效和肝毒性:结果:αCD137-PBNPs分别保留了PBNPs和αCD137的光热和激动特性。在体内,与对照组相比,接受αCD137-PBNP-PTT治疗的SM1肿瘤小鼠的存活率显著提高(50%),且无肝毒性:这些数据表明,将 PBNP-PTT 与基于 αCD137 的激动剂共定位作为一种新型组合纳米药物具有潜在的实用性。
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