使用基于铁蛋白的蛋白笼进行抗疟药物递送:朝着开发抗疟疾智能疗法迈出的一步。
Antimalarial Delivery with a Ferritin-Based Protein Cage: A Step toward Developing Smart Therapeutics against Malaria.
发表日期:2024 Jul 08
作者:
Shruti Bhatt, Subrata Dasgupta, Chiging Tupe, Cherish Prashar, Utpal Adhikari, Kailash C Pandey, Suman Kundu, Soumyananda Chakraborti
来源:
Parasites & Vectors
摘要:
在过去的二十年中,由于其在生物技术和治疗学中的广泛应用,蛋白质笼的利用率呈指数级增长。在最近的 Covid-19 大流行背景下,基于蛋白笼的支架在疫苗开发中发挥了关键作用。除了疫苗之外,由于其独特的结构和结构稳定性,这些蛋白笼已被证明在各种药物输送应用中具有重要价值。在各种类型的蛋白质笼中,基于铁蛋白的笼在药物递送应用中处于领先地位。这主要归因于它们易于生产、卓越的热稳定性和无毒性质。虽然基于铁蛋白的笼子通常用于抗癌药物输送和造影剂输送,但直到本研究之前,它们在疟疾药物输送中的功效尚未得到探索。在这项研究中,几种抗疟药物被封装在马脾铁蛋白内,并通过实验和计算技术验证了结合和加载过程。这些数据明确地证明了抗疟药物可以轻松地掺入铁蛋白中,而不会破坏其三维结构。采用计算对接和分子动力学模拟来查明铁蛋白内药物结合位点的精确位置。随后对疟原虫的功效测试表明,所开发的纳米缀合物(包含药物-铁蛋白缀合物)在根除寄生虫方面表现出显着的有效性。总之,研究结果强烈表明,基于铁蛋白的载体系统对于抗疟药物输送的未来具有巨大的前景,具有高选择性和有限的副作用。
Over the past two decades, the utilization of protein cages has witnessed exponential growth driven by their extensive applications in biotechnology and therapeutics. In the context of the recent Covid-19 pandemic, protein-cage-based scaffolds played a pivotal role in vaccine development. Beyond vaccines, these protein cages have proven valuable in diverse drug delivery applications thanks to their distinctive architecture and structural stability. Among the various types of protein cages, ferritin-based cages have taken the lead in drug delivery applications. This is primarily attributed to their ease of production, exceptional thermal stability, and nontoxic nature. While ferritin-based cages are commonly employed in anticancer drug delivery and contrast agent delivery, their efficacy in malarial drug delivery had not been explored until this study. In this investigation, several antimalarial drugs were encapsulated within horse spleen ferritin, and the binding and loading processes were validated through both experimental and computational techniques. The data unequivocally demonstrate the facile incorporation of antimalarial drugs into ferritin without disrupting its three-dimensional structure. Computational docking and molecular dynamics simulations were employed to pinpoint the precise location of the drug binding site within ferritin. Subsequent efficacy testing on Plasmodium revealed that the developed nanoconjugate, comprising the drug-ferritin conjugate, exhibited significant effectiveness in eradicating the parasite. In conclusion, the findings strongly indicate that ferritin-based carrier systems hold tremendous promise for the future of antimalarial drug delivery, offering high selectivity and limited side effects.