Laboratory of Inflammatory and Neoplastic Cells/Laboratory of Sulfated Polysaccharides Investigation, Cell Biology Department, Section of Biological Sciences, Universidade Federal do Paraná (UFPR), Av Cel Francisco H dos Santos, s/n, CEP 81530-980 Curitiba, PR, Brazil.
Catalysis and Chemical Reactivity Group, Institute of Chemistry and Biotechnology, Universidade Federal de Alagoas, Av. Lourival de Melo Mota, s/n, CEP 57072-900 Maceió, AL, Brazil.
Int J Biol Macromol. 2021 Aug 31;185:551-561. doi: 10.1016/j.ijbiomac.2021.06.172. Epub 2021 Jun 30.
Advanced melanoma patients that are not included in common genetic classificatory groups lack effective and safe therapeutic options. Chemotherapy and immunotherapy show unsatisfactory results and devastating adverse effects for these called triple wild-type patients. New approaches exploring the intrinsic antitumor properties of gold nanoparticles might reverse this scenario as a safer and more effective alternative. Therefore, we investigated the efficacy and safety of a composite made of gum arabic-functionalized gold nanorods (GA-AuNRs) against triple wild-type melanoma. The natural polymer gum arabic successfully stabilized the nanorods in the biological environment and was essential to improve their biocompatibility. In vivo results obtained from treating triple wild-type melanoma-bearing mice showed that GA-AuNRs remarkably reduced primary tumor growth by 45%. Furthermore, GA-AuNRs induced tumor histological features associated with better prognosis while also reducing superficial lung metastasis depth and the incidence of intrapulmonary metastasis. GA-AuNRs' efficacy comes from their capacity to reduce melanoma cells ability to invade the extracellular matrix and grow into colonies, in addition to a likely immunomodulatory effect induced by gum arabic. Additionally, a broad safety investigation found no evidence of adverse effects after GA-AuNRs treatment. Therefore, this study unprecedentedly reports GA-AuNRs as a potential nanomedicine for advanced triple wild-type melanomas.
对于那些不属于常见遗传分类群体的晚期黑色素瘤患者，缺乏有效和安全的治疗选择。化疗和免疫疗法对这些所谓的三野生型患者的效果并不理想，且具有破坏性的副作用。探索金纳米棒固有抗肿瘤特性的新方法可能会改变这种局面，成为一种更安全、更有效的替代方法。因此，我们研究了由阿拉伯胶功能化金纳米棒（GA-AuNRs）组成的复合材料对三野生型黑色素瘤的疗效和安全性。天然聚合物阿拉伯胶成功地在生物环境中稳定了纳米棒，对于提高其生物相容性至关重要。从治疗三野生型黑色素瘤荷瘤小鼠获得的体内结果表明，GA-AuNRs 可显著将原发性肿瘤生长减少 45%。此外，GA-AuNRs 诱导与更好预后相关的肿瘤组织学特征，同时还减少了肺表面转移的深度和肺内转移的发生率。GA-AuNRs 的疗效来自于其降低黑色素瘤细胞侵袭细胞外基质和形成菌落的能力，以及阿拉伯胶可能诱导的免疫调节作用。此外，广泛的安全性研究发现，GA-AuNRs 治疗后没有不良反应的证据。因此，本研究前所未有地报道了 GA-AuNRs 作为一种有潜力的纳米医学方法，可用于治疗晚期三野生型黑色素瘤。
