增强多发性骨髓瘤的精准治疗

Ruogu Qi, Shanshan Wang, Jiayi Yu, Tianming Lu, Zhiqiang Bi, Weibo Liu, Yuanyuan Guo, Yong Bian, Jianliang Shen, Xuesong Zhang, Wenhao Hu

工程（英文） ›› 2024, Vol. 36 ›› Issue (5) : 178-192.

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工程（英文） ›› 2024, Vol. 36 ›› Issue (5) : 178-192. DOI: 10.1016/j.eng.2024.01.001
研究论文
Article

增强多发性骨髓瘤的精准治疗

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Enhanced Precision Therapy of Multiple Myeloma Through Engineered Biomimetic Nanoparticles with Dual Targeting

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摘要

多发性骨髓瘤（MM）是第二大最常见的血液恶性肿瘤。目前，多发性骨髓瘤的治疗策略受到全身毒性大和治疗效果不佳等的阻碍。本研究通过开发一种强效的MM靶向化疗纳米粒子T-PB@M来克服这些局限性，该策略巧妙利用阿伦磷酸盐对骨基质中羟基磷灰石的高亲和力，以及对骨髓瘤细胞膜的同源靶向作用，实现了对肿瘤细胞的精准打击。此外，该纳米粒子能够在低pH环境下智能触发药物释放，实现药物的按需释放，从而提高治疗效果并减少副作用。T-PB@M还能够通过激活PARP1-Caspase3-Bcl2通路，在MM细胞中有效诱导活性氧的产生，进而触发细胞凋亡。值得一提的是，T-PB@M能优先靶向涉及骨骼的部位，有效避免了全身毒性副作用的发生，显著延长了MM原位小鼠的生存期，为临床上MM的精准治疗提供了一个充满前景且极具潜力的平台。

Abstract

Multiple myeloma (MM) is the second most prevalent hematological malignancy. Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy. This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy, which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes, termed T-PB@M. The results from our investigations highlight the considerable bone affinity of T-PB@M, both in vitro and in vivo. Additionally, this material demonstrated a capability for drug release triggered by low pH conditions. Moreover, T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose) polymerase 1 (PARP1)-Caspase-3-B-cell lymphoma-2 (Bcl-2) pathway in MM cells. Notably, T-PB@M preferentially targeted bone-involved sites, thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice. Therefore, this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

关键词

多发性骨髓瘤 / 硼替佐米 / 药物递送 / 双重靶向 / 可控释放

Keywords

Multiple myeloma / Bortezomib / Drug delivery / Dual targeting / Controlled release

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Ruogu Qi, Shanshan Wang, Jiayi Yu. 具有双重靶向功能的工程仿生纳米粒子增强多发性骨髓瘤的精准治疗. Engineering. 2024, 36(5): 178-192 https://doi.org/10.1016/j.eng.2024.01.001

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