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双十二烷聚氧乙烯醚 20 纳米点载 PI3K 抑制剂 LY294002 用于体外和体内 LoVo 细胞的温和光热治疗。

Bi S -Tween 20 Nanodots Loading PI3K Inhibitor, LY294002, for Mild Photothermal Therapy of LoVo Cells In Vitro and In Vivo.

机构信息

College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China.

Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.

出版信息

Adv Healthc Mater. 2018 Nov;7(22):e1800830. doi: 10.1002/adhm.201800830. Epub 2018 Sep 21.

DOI:10.1002/adhm.201800830
PMID:30240165
Abstract

Although various types of photothermal agents are developed for photothermal cancer therapy, relatively few photothermal agents exhibit high tumor inhibition rate under relatively mild conditions. Herein, a multifunctional Bi S -Tween 20 nanoplatform loaded with PI3K inhibitor LY294002 is designed as a novel photothermal agent for inhibitor and photothermal synergistic therapy of tumors under mild photothermal therapy conditions. The LY294002 of PI3K inhibitor, after being loaded by Bi S -Tween 20 nanodots, exhibits greatly increased drug utilization and reduced side effects on normal tissues. In vivo, Bi S -Tween 20@LY294002 upon near-infrared 808 nm laser irradiation shows potent antitumor activity under relatively mild conditions (power density: 0.6 W cm ). Moreover, the mechanism studies also demonstrate that Bi S -Tween 20@LY294002 potently kills LoVo cancer cells under low-power near-infrared light irradiation, by downregulating the expression of heat shock protein 70 (HSP70) so as to increase the sensitivity of tumor cell hyperthermia and activating BAX/BAK-regulated mitochondrial apoptosis pathway. The results demonstrate that the newly synthesized multifunctional nanoplatform paves a new avenue for accurate therapy of photothermal-resistant cancer.

摘要

尽管已经开发出了各种类型的光热试剂用于光热癌症治疗,但在相对温和的条件下,能够表现出高肿瘤抑制率的光热试剂相对较少。在此,设计了一种多功能 Bi S -Tween 20 纳米平台,负载 PI3K 抑制剂 LY294002,作为一种新型光热试剂,用于在温和的光热治疗条件下对肿瘤进行抑制剂和光热协同治疗。PI3K 抑制剂 LY294002 被 Bi S -Tween 20 纳米点负载后,药物利用率大大提高,对正常组织的副作用降低。在体内,近红外 808nm 激光照射下的 Bi S -Tween 20@LY294002 在相对温和的条件下(功率密度:0.6 W cm )表现出强大的抗肿瘤活性。此外,机制研究还表明,Bi S -Tween 20@LY294002 通过下调热休克蛋白 70(HSP70)的表达,在低功率近红外光照射下强力杀死 LoVo 癌细胞,从而提高肿瘤细胞热疗的敏感性,并激活 BAX/BAK 调节的线粒体凋亡途径。结果表明,新合成的多功能纳米平台为光热耐药性癌症的精确治疗开辟了新途径。

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