Suramin (SM), a drug for African sleeping sickness and river blindness therapy, has been investigated in various clinical trials for cancer therapy. However, SM was eventually withdrawn from the market because of its narrow therapeutic window and the side effects associated with multiple targets. In this work, we developed a simple but effective system based on a nontoxic dose of SM combined with a chemotherapeutic agent for the treatment of metastatic triple-negative breast cancer (TNBC). SM and glycol chitosan (GCS) formed nanogels because of the electrostatic effect, whereas doxorubicin (DOX) was incorporated into the system through the hydrophilic and hydrophobic interactions between DOX and GCS as well as the ionic interactions between DOX and SM to yield GCS-SM/DOX nanoparticles (NPs). GCS-SM/DOX NPs have a size of approximately 186 nm and a spherical morphology. In vitro experiments showed that GCS-SM NPs could effectively inhibit cancer cell migration and invasion, as well as angiogenesis. Furthermore, in a TNBC lung metastasis animal model, GCS-SM/DOX NPs significantly reduced tumor burden and extended the lifespan of animals, while not inducing cardio and renal toxicities associated with the DOX and SM, respectively. As all the components used in this system are biocompatible and easy for large-scale fabrication, the GCS-SM/DOX system is highly translatable for the metastatic breast cancer treatment. STATEMENT OF SIGNIFICANCE: The doxorubicin-loaded glycol chitosan-suramin nanoparticle (GCS-SM/DOX) is novel in the following aspects: SM acts as not only a gelator for the first time in the preparation of the nanoparticle but also an active pharmaceutical agent in the dosage form. GCS-SM/DOX NP significantly reduced tumor burden and extended the lifespan of animals with triple-negative breast cancer lung metastasis. GCS-SM/DOX NPs attenuate cardio and renal toxicities associated with the DOX and SM. The GCS-SM/DOX system is highly translatable because of its simple, one-pot, and easy-to-scale-up preparation protocol.

中文翻译：

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用基于壳聚糖的纳米粒子重新应用苏拉明治疗乳腺癌的肺转移。

Suramin（SM）是用于非洲昏睡病和河盲症治疗的药物，已在各种癌症治疗的临床试验中进行了研究。然而，由于SM的狭窄治疗窗口以及与多个靶标相关的副作用，SM最终退出了市场。在这项工作中，我们开发了一种简单但有效的系统，该系统基于无毒剂量的SM结合化学治疗剂来治疗转移性三阴性乳腺癌（TNBC）。SM和乙二醇壳聚糖（GCS）由于静电作用而形成纳米凝胶，而阿霉素（DOX）通过DOX和GCS之间的亲水和疏水相互作用以及DOX和SM之间的离子相互作用被引入系统中，从而生成GCS-SM / DOX纳米粒子（NPs）。GCS-SM / DOX NP的大小约为186 nm，呈球形。体外实验表明，GCS-SM NPs可以有效抑制癌细胞的迁移和侵袭以及血管生成。此外，在TNBC肺转移动物模型中，GCS-SM / DOX NP显着降低了肿瘤负担并延长了动物的寿命，而没有分别引起与DOX和SM相关的心脏和肾脏毒性。由于该系统中使用的所有组件均具有生物相容性且易于大规模制造，因此GCS-SM / DOX系统可高度转移用于转移性乳腺癌治疗。意义声明：载有阿霉素的乙二醇壳聚糖-苏拉明纳米颗粒（GCS-SM / DOX）在以下方面具有新颖性：SM不仅在纳米颗粒的制备中首次充当胶凝剂，而且在剂型中还充当活性药物。GCS-SM / DOX NP显着降低了肿瘤负担，并延长了三阴性乳腺癌肺转移动物的寿命。GCS-SM / DOX NP减弱了与DOX和SM相关的心脏和肾脏毒性。GCS-SM / DOX系统具有简单，一锅式且易于扩展的制备方案，因此具有很高的可翻译性。