High-specificity drug uptake using magneto-electric nanoparticles for cancer treatment

人体循环系统可以将药物输送到体内的每一个细胞；然而，将药物带入肿瘤细胞而不影响健康细胞仍然是一项艰巨的任务。一种能够高特异性输送抗肿瘤药物的技术的可用性将是癌症研究的一个突破。这项研究的目的是进行基础的体外和体内研究，以了解载药磁电纳米颗粒(MEN)在高度局部肿瘤部位的潜在物理学基础。工程方法在于通过施加低能量磁场增加细胞膜的孔隙率，使药物能够渗透到癌细胞内部，而不会影响周围的健康细胞。建议的方法将形成一种新的外场控制程序的基础，用于治疗各种癌症，包括卵巢癌、乳腺癌和肺癌。该项目的一个重要目标是激励学生，特别是FIU和南佛罗里达的少数族裔代表不足的学生，在纳米工程和医学的交叉点攻读跨学科学位。跨学科研究团队包括一名电气工程师、一名妇科肿瘤学家、一名临床药理学家和一名细胞生物学家。在卵巢癌中，通过外科植入的导管进行腹膜内分娩显示了更高的存活率。然而，导管的并发症和毒性阻碍了这项技术的广泛采用。在这项研究中，提出了一种新的纳米技术，以利用(I)癌细胞和健康细胞膜电学性质的差异，以及(Ii)磁电纳米颗粒(MEN)在体温下作为局部磁场的局域转换能力，将远程提供的磁场转化为人类的本征电场，从而触发局部纳米电穿孔效应。该技术允许远程控制静脉注射MANS负载药物附近的电场，从而能够以所需的针对肿瘤细胞的特异性递送药物。电穿孔将被用来通过施加足够高的电场将药物输送到细胞内，以克服增加药物在细胞内渗透的孔隙率所需的阈值。所需的特异性是由于癌细胞的阈值比健康细胞的阈值低至少两倍。扫描探针显微镜和综合表面光谱学将被用来了解人在不同野外条件下与癌症和健康细胞微环境相互作用的药代动力学和药效学。卵巢癌将作为一个模型，以纳米粒子为核心，以钛酸钴和钛酸钡为核壳，联合紫杉醇作为一种流行的有丝分裂抑制药物。将使用标准化验方法来研究不同现场条件下男性的毒性。将利用小鼠动物模型进行体内研究。

The human circulatory system can deliver a drug to every cell in the body; however, bringing a drug inside a tumor cell without affecting the healthy cells remains a formidable task. Availability of a technology capable of high-specificity delivery of anti-neoplastic drugs would be a breakthrough in cancer research. The objective of this research is to conduct basic in-vitro and in-vivo studies to understand the underlying physics of drug-loaded magneto-electric nanoparticles (MENs) at highly localized tumor sites. The engineering approach lies in increasing the porosity of the cell membrane, via application of a low-energy magnetic field, to allow the drug to penetrate inside the cancer cells without affecting the surrounding healthy cells. The proposed approach will form a basis of a novel external-field-controlled procedure to treat various cancers, including ovarian, breast and lung. An important goal of the project is to motivate students, especially underrepresented minorities at FIU and in South Florida, to pursue cross-disciplinary degrees at the intersection of nano-engineering and medicine. The interdisciplinary research team includes an electrical engineer, a gynecologic oncologist, a clinical pharmacologist and a cellular biologist. In ovarian cancers, intraperitoneal delivery through a surgically implanted catheter has shown improved survival rates. However, catheter complications and toxicity have precluded widespread adoption of this technique. In this study, a new nanotechnology is proposed to take advantage of (i) the difference between the membrane electric properties of cancer and healthy cells, and (ii) the capability of magneto-electric nanoparticles (MENs) at body-temperature to serve as localized converters of a remotely supplied magnetic field into the MENs' intrinsic electric fields that can trigger local nano-electroporation effects. The technique allows to remotely control the electric fields in the vicinity of intravenously injected MENs-loaded drug and consequently to enable drug delivery with required specificity to the tumor cells. Electroporation will be used to deliver a drug inside the cytosol via application of high enough electric field to overcome the threshold required for increasing the porosity for drug penetration inside the cell. The required specificity is due to the lower threshold of the cancer cells being by at least a factor of two than that of the healthy cells. Scanning probe microscopy and comprehensive surface spectroscopy will be used to understand the pharmacokinetics and pharmacodynamics of the MENs' interaction with both the cancer and healthy cellular microenvironment under different field conditions. Ovarian cancer will be used as a model with nanoparticles core shell of cobalt iron titanate and barium titatnate as basic MENs in conjunction with paclitaxel as a popular mitotic inhibitor drug. Standard assays will be used to study the MENs' toxicity under different field conditions. A mouse animal model will be exploited to conduct in-vivo studies.