Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021:4230-4233. doi: 10.1109/EMBC46164.2021.9630862.
MicroRNA-based gene therapy for cancer treatment via nanoparticles (NPs) requires navigation of multiple physical and physiological barriers in order to efficiently deliver the miRNAs to the cancer cell cytoplasm. We here present a mathematical model to investigate the variability associated with tumor, NP, and miRNA characteristics, and identify the limiting factors in miRNA delivery to tumors. Through global parameter analysis, the miRNA release rate from NPs and NP degradability were found to have the most significant impact on cytosolic accumulation of miRNAs. These NP properties can be fine-tuned in order to optimize the delivery system for enhancing the efficacy of miRNA-based therapy.Clinical Relevance-Understanding the effect of nanoparticle, tumor, and miRNA characteristics in governing the efficacy of miRNA-based cancer therapy will support its clinical translation.
基于 miRNA 的癌症治疗基因疗法需要克服多种物理和生理屏障，以便将 miRNAs 有效地递送到癌细胞细胞质中。我们在这里提出了一个数学模型来研究与肿瘤、NP 和 miRNA 特征相关的可变性，并确定 miRNA 递送到肿瘤中的限制因素。通过全局参数分析，发现从 NPs 中释放 miRNA 的速率和 NP 的降解性对 miRNA 在细胞质中的积累有最显著的影响。可以对这些 NP 特性进行微调，以优化递送系统，增强 miRNA 为基础的治疗效果。临床意义-理解纳米粒子、肿瘤和 miRNA 特征在控制 miRNA 为基础的癌症治疗效果中的作用，将支持其临床转化。
