Solid cancer remains a serious threat to global health despite decades of progress. Traditional chemotherapy treatment has been used to curb the disease despite its inability to reach cancer cells at high enough quantities leading to adverse toxicity on healthy cells, producing severe side effects, and exacerbating patient suffering. Active targeted nano-drugs (ATNDs) acting as transporter systems have become a viable solution to this shortcoming, offering the possibility of more precise cancer targeting. Therefore, in the present study, we develop a numerical model of capturing ATNDs, incorporating movements within and outside the tumor spheroid and the magnetic forces guiding the nanoparticles. By combining a model of ATNDs transport with a tumor-effector dynamic model based on porous media phenomena, we demonstrate how the models may be combined to model drug-loaded nanoparticle transport in an external magnetic field. We analyze the controlled drug delivery against traditional chemotherapy based on the combined effect of immunotherapy and chemotherapy with the dispersion of nano-drugs to lead a solute cloud toward the tumor. We found that the amalgamation of immune and chemotherapy delivered by ATNDs enhances cancer therapy efficacy compared with conventional chemotherapy. Increased drug convection toward the tumor region presented by ascending values of the Peclet number inhibits the growth of tumor cells and prolongs progression-free survival. Increases in source term and vessel permeability also increase the likelihood of tumor suppression, while raising the hematocrit and magnetic number results in reduced tumor cell killing. Sensitivity analysis of the dynamic model parameters has been discussed. This work demonstrates that ATND-delivery systems can improve therapeutic agent delivery to the tumor tissue, and promote tumor cell killing.

中文翻译：

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化疗-免疫联合治疗期间药物分散对肿瘤效应动力学的影响及敏感性分析


尽管取得了数十年的进展，实体癌症仍然对全球健康构成严重威胁。传统的化疗治疗已被用来遏制这种疾病，尽管它无法达到足够数量的癌细胞，导致对健康细胞产生不良毒性，产生严重的副作用，并加剧患者的痛苦。作为转运系统的活性靶向纳米药物（ATND）已成为解决这一缺点的可行解决方案，为更精确的癌症靶向提供了可能性。因此，在本研究中，我们开发了一种捕获 ATND 的数值模型，其中结合了肿瘤球体内部和外部的运动以及引导纳米粒子的磁力。通过将 ATND 运输模型与基于多孔介质现象的肿瘤效应器动态模型相结合，我们演示了如何组合这些模型来模拟外部磁场中载药纳米颗粒的运输。我们基于免疫疗法和化疗的联合作用以及纳米药物的分散将溶质云引向肿瘤来分析针对传统化疗的受控药物递送。我们发现，与传统化疗相比，ATND 提供的免疫和化疗的结合增强了癌症治疗效果。佩克莱特数的上升值呈现增加的药物对肿瘤区域的对流，抑制肿瘤细胞的生长并延长无进展生存期。源项和血管通透性的增加也增加了肿瘤抑制的可能性，同时血细胞比容和磁数的增加导致肿瘤细胞杀伤减少。讨论了动态模型参数的敏感性分析。 这项工作表明 ATND 递送系统可以改善治疗剂向肿瘤组织的递送，并促进肿瘤细胞杀伤。