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通过电纺纳米纤维膜共递送小干扰RNA(siRNA)和顺铂用于恶性黑色素瘤的协同治疗

Co-delivery of siRNA and cisplatin via electrospun Nanofibrous membranes for synergistic treatment of malignant melanoma.

作者信息

Zhang Xuewei, Zheng Guoxing, Zhou Zibin, Zhu Mingyu, Tang Shijie

机构信息

Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515000, China.

Department of Spine Surgery, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515000, China.

出版信息

Heliyon. 2024 Sep 6;10(17):e37517. doi: 10.1016/j.heliyon.2024.e37517. eCollection 2024 Sep 15.

Abstract

Tumor recurrence and metastasis remain formidable challenges in clinical oncology. Although surgery is an effective treatment for early-stage solid tumors, residual cancer cells can lead to subsequent recurrence or metastasis. Conventional treatments for melanoma, such as anti-tumor medications and gene therapy, have distinct limitations. The rapid systemic distribution of anti-tumor drugs poses a significant challenge, often resulting in notable side effects and inadequate drug concentrations at the tumor site. Melanoma (MM), a deadly form of skin cancer, is known for its high mortality rate. In this study, we propose a novel strategy for treating MM by combining the controlled release of chemotherapeutic drugs encapsulated within Metal-Organic Frameworks (MOFs) and liposomes with gene therapy targeting Minichromosome Maintenance Proteins 4 (MCM4) using electrospinning and surface modification techniques. and results confirmed that this hierarchical membrane system can effectively deliver therapeutic MCM4 siRNA and release cisplatin to inhibit tumor growth. Furthermore, we demonstrated that MCM4 silencing promoted the sensitivity of melanoma cells to ferroptosis both and . The proposed strategy, by allowing for a controlled and sustained release of medication, could alleviate the challenges in drug delivery and aid in prevent tumor recurrence.

摘要

肿瘤复发和转移仍然是临床肿瘤学中严峻的挑战。尽管手术是早期实体瘤的有效治疗方法,但残留的癌细胞会导致随后的复发或转移。黑色素瘤的传统治疗方法,如抗肿瘤药物和基因治疗,都有明显的局限性。抗肿瘤药物的快速全身分布带来了重大挑战,常常导致显著的副作用以及肿瘤部位药物浓度不足。黑色素瘤(MM)是一种致命的皮肤癌形式,以其高死亡率而闻名。在本研究中,我们提出了一种治疗黑色素瘤的新策略,即通过静电纺丝和表面改性技术,将封装在金属有机框架(MOF)和脂质体中的化疗药物的控释与靶向微小染色体维持蛋白4(MCM4)的基因治疗相结合。结果证实,这种分级膜系统可以有效地递送治疗性MCM4 siRNA并释放顺铂以抑制肿瘤生长。此外,我们还证明,MCM4沉默在体内和体外均促进了黑色素瘤细胞对铁死亡的敏感性。所提出的策略通过实现药物的控释和持续释放,可以缓解药物递送方面的挑战并有助于预防肿瘤复发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d6e/11407083/70ee12302dfb/gr1.jpg

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