To meet the current need for a tumor-selective, targeted therapy regimen associated with reduced toxicity, our laboratory has developed a spontaneously assembled nanostructure that resembles high-density lipoproteins (HDLs). These myristoyl-5A (MYR-5A) nanotransporters are designed to safely transport lipophilic pharmaceuticals, including a novel anthracycline drug (N-benzyladriamycin-14-valerate (AD198)). This formulation has been found to enhance the therapeutic efficacy and reduced toxicity of drugs in preclinical studies of 2D and 3D models of Ewing sarcoma (EWS) and cardiomyocytes. Our findings indicate that the MYR-5A/AD198 nanocomplex delivers its payload selectively to cancer cells via the scavenger receptor type B1 (SR-B1), thus providing a solid proof of concept for the development of an improved and highly effective, potentially personalized therapy for EWS while protecting against treatment-associated cardiotoxicity.

中文翻译：

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自发组装脂肽纳米缀合物转运蒽环类药物 N-Benzyladriamycin-14-valerate 用于尤文肉瘤的个性化治疗

为了满足当前对肿瘤选择性、降低毒性的靶向治疗方案的需求，我们的实验室开发了一种类似于高密度脂蛋白（HDL）的自发组装纳米结构。这些肉豆蔻酰-5A (MYR-5A) 纳米转运蛋白旨在安全运输亲脂性药物，包括新型蒽环类药物（N -benzyladriamycin-14-valerate (AD198)）。在尤文肉瘤 (EWS) 和心肌细胞的 2D 和 3D 模型的临床前研究中，发现该配方可以增强药物的治疗效果并降低药物的毒性。我们的研究结果表明，MYR-5A/AD198 纳米复合物通过 B1 型清道夫受体 (SR-B1) 选择性地将其有效负载传递给癌细胞，从而为开发改进的、高效的、潜在的个性化疗法提供了坚实的概念证明。用于 EWS，同时防止治疗相关的心脏毒性。