Synergistic administration of photothermal therapy and chemotherapy to cancer cells using polypeptide-based degradable plasmonic matrices.
Synergistic administration of photothermal therapy and chemotherapy to cancer cells using polypeptide-based degradable plasmonic matrices.
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DOI：
10.2217/nnm.10.133
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Rege K
中科院分区：
文献类型：
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作者：
Huang HC;Yang Y;Nanda A;Koria P;Rege K
癌细胞对高热温度的抗性和纳米颗粒诱导的高热的空间限制需要鉴定可以增强这种治疗的功效的有效组合治疗。在这里，我们表明，新的多肽为基础的可降解等离子体基质可用于同时管理的热疗和化疗药物作为一种有效的组合治疗，可以克服癌细胞耐高温。新的金纳米棒弹性蛋白样多肽基质的产生和表征。基质还装载有热休克蛋白（HSP）90抑制剂17-（烯丙基氨基）-17-去甲氧基格尔德霉素（17-AAG），目前在不同恶性肿瘤的临床试验中，以提供热疗和化疗的组合。在等离子体基质（没有17-AAG）上培养的细胞的激光照射导致直接在激光路径中的细胞死亡，而在激光路径之外的细胞没有显示出任何活力损失。这样的空间限制，与促存活热休克蛋白的表达一致，降低了热疗的疗效。17-AAG-金纳米棒-多肽基质显示药物对周围介质的最小浸出。高温和17-AAG从基质中释放的组合（两者都由激光照射诱导）导致癌细胞的显著（>90%）死亡，而“单一处理”（即，单独的热疗和单独的17-AAG）显示最小的癌细胞活力损失（<10%）。同时施用热疗和从等离子体基质释放HSP抑制剂是用于消融恶性细胞的有力方法，并且可以扩展到用于各种恶性肿瘤的纳米颗粒和化疗药物的不同组合。
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.