Hoopes Pj, Tate Ja, Ogden Ja, Strawbridge Rr, Fiering Sn, Petryk Aa, Cassim Sm, Giustini Aj, Demidenko E, Ivkov R, Barry S, Chinn P, Foreman A
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755 USA ; Dartmouth Medical School, Hanover, NH 03755 USA.
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755 USA.
Proc SPIE Int Soc Opt Eng. 2009 Feb 23;7181:71810P. doi: 10.1117/12.812056.
Hyperthermia, as an independent modality or in combination with standard cancer treatments such as chemotherapy and radiation, has been established and as an effective cancer treatment. However, despite efforts over the past 25 years, such therapies have never been optimized or widely-accepted clinically. Although methods continue to improve, conventionally-delivered heat (RF, ultrasound, microwave etc) can not be delivered in a tumor selective manner. The development of antibody-targeted, or even nontargeted, biocompatible iron oxide nanoparticles (IONP) now allows delivery of cytotoxic heat to individual cancer cells. Using a murine mouse mammary adenocarcinoma (MTGB) and human colon carcinoma (HT29) cells, we studied the biology and treatment of IONP hyperthermia tumor treatment.
Cancer cells (1 × 10) with or without iron oxide nanoparticles (IONP) were studied in culture or in vivo via implanted subcutaneously in female C3H mice, Tumors were grown to a treatment size of 150 mm and tumors volumes were measured using standard 3-D caliper measurement techniques. Mouse tumors were heated via delivery of an alternating magnetic field, which activated the nanoparticles, using a cooled 36 mm diameter square copper tube induction coil which provided optimal heating in 1.5 cm wide region of the coil. The IONPs were dextran coated and had a hydrodynamic radius of approximately 100 nm. For the in vivo studies, intra-tumor, peritumor and rectal (core body) temperatures were continually measured throughout the treatment period.
Although some eddy current heating was generated in non-target tissues at the higher field strengths, our preliminary IONP hyperthermia studies show that whole mouse AMF exposure @160 KHz and 400 or 550 Oe, for a 20 minutes (heat-up and protocol heating), provides a safe and efficacious tumor treatment. Initial electron and light microscopic studies ( and ) showed the 100 nm used in our studies are rapidly taken up and retained by the tumor cells. Additional in vitro studies suggest antibodies can significantly enhance the cellular uptake of IONPs.
热疗作为一种独立的治疗方式，或与化疗和放疗等标准癌症治疗方法联合使用，已被确立为一种有效的癌症治疗方法。然而，尽管在过去25年中付出了努力，但此类疗法从未在临床上得到优化或广泛接受。尽管方法不断改进，但传统方式传递的热量（射频、超声、微波等）无法以肿瘤选择性的方式传递。抗体靶向甚至非靶向的生物相容性氧化铁纳米颗粒（IONP）的发展，现在使得细胞毒性热量能够传递到单个癌细胞。我们使用小鼠乳腺腺癌（MTGB）和人结肠癌细胞（HT29），研究了IONP热疗肿瘤治疗的生物学特性和治疗效果。
将含有或不含氧化铁纳米颗粒（IONP）的癌细胞（1×10）在培养物中或通过皮下植入雌性C3H小鼠体内进行研究，肿瘤生长至150立方毫米的治疗大小，并使用标准的三维卡尺测量技术测量肿瘤体积。通过施加交变磁场加热小鼠肿瘤，该交变磁场激活纳米颗粒，使用冷却的直径36毫米的方形铜管感应线圈，该线圈在1.5厘米宽的线圈区域内提供最佳加热效果。IONP用葡聚糖包被，流体动力学半径约为100纳米。对于体内研究，在整个治疗期间持续测量肿瘤内、肿瘤周围和直肠（核心体温）温度。
尽管在较高场强下非靶组织中会产生一些涡电流加热，但我们初步的IONP热疗研究表明，在160千赫兹和400或550奥斯特的交变磁场下，对整个小鼠进行20分钟（升温及方案加热）的暴露，可提供安全有效的肿瘤治疗。最初的电子显微镜和光学显微镜研究表明，我们研究中使用的100纳米颗粒被肿瘤细胞迅速摄取并保留。额外的体外研究表明，抗体可显著增强IONP的细胞摄取。
