Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA.
Nanomedicine (Lond). 2011 Apr;6(3):459-73. doi: 10.2217/nnm.10.133.
Resistance of cancer cells to hyperthermic temperatures and spatial limitations of nanoparticle-induced hyperthermia necessitates the identification of effective combination treatments that can enhance the efficacy of this treatment. Here we show that novel polypeptide-based degradable plasmonic matrices can be employed for simultaneous administration of hyperthermia and chemotherapeutic drugs as an effective combination treatment that can overcome cancer cell resistance to hyperthermia.
Novel gold nanorod elastin-like polypeptide matrices were generated and characterized. The matrices were also loaded with the heat-shock protein (HSP)90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), currently in clinical trials for different malignancies, in order to deliver a combination of hyperthermia and chemotherapy.
Laser irradiation of cells cultured over the plasmonic matrices (without 17-AAG) resulted in the death of cells directly in the path of the laser, while cells outside the laser path did not show any loss of viability. Such spatial limitations, in concert with expression of prosurvival HSPs, reduce the efficacy of hyperthermia treatment. 17-AAG-gold nanorod-polypeptide matrices demonstrated minimal leaching of the drug to surrounding media. The combination of hyperthermic temperatures and the release of 17-AAG from the matrix, both induced by laser irradiation, resulted in significant (>90%) death of cancer cells, while 'single treatments' (i.e., hyperthermia alone and 17-AAG alone) demonstrated minimal loss of cancer cell viability (<10%).
Simultaneous administration of hyperthermia and HSP inhibitor release from plasmonic matrices is a powerful approach for the ablation of malignant cells and can be extended to different combinations of nanoparticles and chemotherapeutic drugs for a variety of malignancies.
癌细胞对高热温度的抗性和纳米颗粒诱导的热疗的空间限制，需要确定有效的联合治疗方法，以提高这种治疗的效果。在这里，我们展示了新型多肽可降解等离子体基质可用于同时给予热疗和化疗药物，作为一种有效的联合治疗方法，可以克服癌细胞对热疗的抗性。
制备并表征了新型金纳米棒弹性蛋白样多肽基质。还将热休克蛋白（HSP）90 抑制剂 17-（烯丙基氨基）-17-去甲氧基格尔德霉素（17-AAG）载入基质中，用于提供热疗和化疗的联合治疗。
在等离子体基质（无 17-AAG）上培养的细胞进行激光照射，导致激光路径直接的细胞死亡，而激光路径之外的细胞没有显示出任何活力丧失。这种空间限制与 prosurvival HSP 的表达一起，降低了热疗的效果。17-AAG-金纳米棒-多肽基质显示出药物向周围介质的最小浸出。由激光照射诱导的热疗温度升高和 17-AAG 从基质中的释放的组合导致癌细胞的显著死亡（>90%），而“单一治疗”（即单独热疗和单独 17-AAG）仅导致癌细胞活力的最小损失（<10%）。
同时给予热疗和 HSP 抑制剂从等离子体基质中释放是一种用于消融恶性细胞的有效方法，并且可以扩展到不同的纳米颗粒和化疗药物的组合，用于各种恶性肿瘤。
