新型冻干/重组血小板产品给药阿霉素具有抗癌活性

Adrienne M. P. Wright, Ying Yi Zheng, Amber Lee, Braden Ishler, Daniel A Sheik, Keith A Moskowitz, Mark L Weiss
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引用次数: 0

摘要

背景:癌症是一个全球性的健康问题,每年有数百万人被诊断出癌症。尽管化疗有毒副作用,但它仍然是许多癌症的主要治疗方法。目前,开发纳米颗粒系统以提高化疗药物的特异性和效率是人们关注的焦点。生物给药方法,例如血小板,与传统的合成纳米颗粒相比具有优势,并且可以通过避免免疫相互作用来增强治疗效力。血小板是一种潜在的药物递送生物纳米颗粒来源,但其短暂的保质期限制了其治疗潜力。冻干已被用于增加血小板的保质期和稳定性。方法:在这里,我们评估了Cellphire专有的冷冻干燥血小板产品的改良版本,该产品装载细胞毒性药物阿霉素,用于输送到血管肉瘤细胞。结果:我们证明,1-10%体积/体积(v/v)添加到血管肉瘤培养物中,负载阿霉素的冻干人血小板(DOX-LHP)通过抑制增殖、代谢和促进细胞凋亡具有有效的抗癌活性。此外,与含有5µM游离阿霉素的培养基处理的细胞相比,暴露于5% v/v DOX-LHP和10% v/v DOX-LHP的血管肉瘤细胞含有2.2倍和4倍的细胞内阿霉素。结论:这些结果表明,冻干的DOX-LHP克服了血小板的储存限制,一旦重组,它们就可以作为细胞毒性化合物的有效药物递送载体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Doxorubicin delivery via novel lyophilized/reconstituted platelet-product has anti-cancer activity
Background: Cancer is a global health concern with millions of people diagnosed annually. Chemotherapy remains the primary treatment for many cancers despite its toxic side effects. Currently, there is focus on developing nanoparticle systems to enhance the specificity and efficiency of chemotherapeutics. Biological drug delivery methods, e.g., platelets, offer advantages compared to traditional, synthetic nanoparticles and may enhance therapeutic potency by avoiding immune interactions. Platelets are a potential source of biological nanoparticles for drug delivery but, their short shelf-life limits their therapeutic potential. Lyophilization has been used to increase the shelf-life and stability of platelets. Methods: Here, we evaluate a modified version of Cellphire’s proprietary freeze-dried platelet product loaded with the cytotoxic drug, doxorubicin, for delivery to hemangiosarcoma cells. Results: We demonstrate that 1-10% volume/volume (v/v) addition of doxorubicin-loaded Lyophilized Human Platelets (DOX-LHP) to hemangiosarcoma cultures have potent anti-cancer activity by inhibiting proliferation, metabolism, and promoting apoptosis. Further, hemangiosarcoma cells exposed to 5% and 10% v/v DOX-LHP contained 2.2x and 4x more intracellular doxorubicin compared to cells treated with media containing 5 µM free doxorubicin. Conclusions: These results suggest that lyophilized, DOX-LHP overcome the storage limitations of platelets and once reconstituted they function as effective drug delivery vehicles for cytotoxic compounds.
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