关键词: Decursin Drug release Elastin Nanogel Prostate cancer therapy

Mesh : Male Elastin / chemistry Humans Cell Line, Tumor Nanogels / chemistry Prostatic Neoplasms, Castration-Resistant / drug therapy pathology metabolism Drug Delivery Systems Cell Survival / drug effects Drug Liberation Antineoplastic Agents / pharmacology chemistry administration & dosage Benzopyrans Butyrates

来  源:   DOI:10.1038/s41598-024-65999-x   PDF(Pubmed)

Abstract:
Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/βcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.
摘要:
纳米凝胶为精确的药物输送提供了希望,而解决药物输送障碍对于有效的前列腺癌(PCa)管理至关重要。我们开发了一种可注射的弹性蛋白纳米凝胶(ENG),用于有效的药物递送系统,通过递送Decursin来克服去势抵抗性前列腺癌(CRPC),一种阻断PCa的Wnt/β连环蛋白途径的小分子抑制剂。ENG表现出良好的特性,如生物相容性,灵活性,和低毒性。在这项研究中,尺寸,形状,表面电荷,化学成分,热稳定性,和ENG的其他特性用于确认成功合成并将Decursin(DEC)掺入到弹性蛋白纳米凝胶(ENG)中用于前列腺癌治疗。体外研究表明,DEC从ENG持续释放超过120小时,具有pH依赖性释放模式。DU145细胞系诱导DEC-ENG的中等细胞毒性表明纳米药物对细胞活力有影响,并有助于在治疗功效和安全性之间取得平衡,而与游离DEC相比,EPR效应能够靶向药物递送至前列腺肿瘤部位。形态学分析进一步支持DEC-ENG诱导细胞死亡的有效性。总的来说,这些发现强调了ENG封装的decurin作为CRPC靶向给药系统的有希望的作用。
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