"Tandem" Nanomedicine Approach against Osteoclastogenesis: Polysulfide Micelles Synergically Scavenge ROS and Release Rapamycin.,Biomacromolecules

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"Tandem" Nanomedicine Approach against Osteoclastogenesis: Polysulfide Micelles Synergically Scavenge ROS and Release Rapamycin.
Biomacromolecules ( IF 5.5 ) Pub Date : 2019-12-17 , DOI: 10.1021/acs.biomac.9b01348
Farah El Mohtadi ₁ , Richard d'Arcy ₂ , Jason Burke ₁ , Julio M Rios De La Rosa ₁ , Arianna Gennari ₂ , Roberto Marotta ₃ , Nora Francini ₂ , Roberto Donno ₂ , Nicola Tirelli _{1,

2}

Affiliation

We show the first example of a synergic approach of oxidant (ROS) scavenging carrier and ROS-responsive drug release in the context of a potential therapy against osteoporosis, aiming to inhibit the differentiation of inflammatory cells into osteoclasts. In our "tandem" approach, a branched amphiphilic, PEGylated polysulfide (PPSES-PEG) was preferred over a linear analogue, because of improved homogeneity in the aggregates (spherical micelles vs mixture of wormlike and spherical), increased stability, and higher drug loading (up to ∼22 wt % of antiosteoclastic rapamycin). These effects are ascribed to the branching inhibiting crystallization in the polysulfide blocks. The ROS-scavenging micelles alone were already able to reduce osteoclastogenesis in a RAW 264.7 model, but the "drug" combination (the polymer itself + rapamycin released only under oxidation) completely abrogated the process. An important take-home message is that the synergic performance depended very strongly on the oxidant:oxidizable group molar ratio, a parameter to carefully tune in the perspective of targeting specific diseases.

中文翻译：

对抗破骨细胞生成的“串联”纳米医学方法：聚硫化物胶束协同清除ROS并释放雷帕霉素。

我们展示了在针对骨质疏松症的潜在疗法的背景下，氧化剂（ROS）清除载体和ROS响应药物释放的协同方法的第一个例子，旨在抑制炎症细胞向破骨细胞的分化。在我们的“串联”方法中，支链两亲，聚乙二醇化多硫化物（PPSES-PEG）比线性类似物更可取，因为它可以改善聚集体的均质性（球形胶束与蠕虫状和球形混合物的稳定性），增加的稳定性和较高的载药量（最多约22 wt％的抗破骨细胞雷帕霉素）。这些作用归因于多硫化物嵌段中的支化抑制结晶。仅ROS清除胶束就已经能够减少RAW 264.7模型中的破骨细胞生成，但是“药物” 这种结合（聚合物本身+雷帕霉素仅在氧化作用下释放）完全废除了该过程。一个重要的提示是，协同性能非常依赖于氧化剂：可氧化基团的摩尔比，这是在针对特定疾病的角度进行仔细调整的参数。

更新日期：2019-12-18

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