Near-infrared light triggers release of Paclitaxel from biodegradable microspheres: photothermal effect and enhanced antitumor activity.

Near-infrared light triggers release of Paclitaxel from biodegradable microspheres: photothermal effect and enhanced antitumor activity.
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DOI:
10.1002/smll.201000028
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发表时间:
2010-05-07
期刊:
影响因子:
13.3
通讯作者:
Li, Chun
Li, Chun
中科院分区:
材料科学1区
文献类型:
--
作者:
You, Jian;Shao, Ruping;Wei, Xin;Gupta, Sanjay;Li, Chun

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尽管在受控药物递送方面取得了进展,但仍需要用于可活化的、高分辨率的药物释放控制的可靠方法。我们假设由近红外(NIR)激光和中空金纳米球(HAuNS)介导的光热效应可以调节抗癌药物的释放。我们通过开发含有抗肿瘤药物紫杉醇(PTX)和HAuNS(直径约35 nm)的生物可降解和生物相容性微球(1~15 µm)来测试这一假设,该微球在近红外(NIR)区域显示表面等离子体吸收。含HAuNS的微球表现出与普通HAuNS相似的近红外光诱导热效应。当用NIR光(808 nm)照射微球时,观察到PTX从含PTX/HAuNS的微球的快速、重复的PTX释放,而当关闭NIR光时,PTX释放变得不显著。PTX从微球中的释放可以通过NIR激光输出功率、激光照射的持续时间、治疗频率和嵌入微球内的HAuNS的浓度来容易地控制。在体外,与PTX/HAuNS负载的微球一起孵育并用NIR光照射的癌细胞显示出比单独与微球一起孵育的细胞或单独用NIR光照射的细胞显著更大的细胞毒性效应,这是由于NIR光触发的药物释放。与用装载有HAuNS的微球(无PTX)和NIR照射或单独用装载有PTX/HAuNS的微球处理的肿瘤相比,用瘤内注射装载有PTX/HAuNS的微球随后NIR照射处理裸鼠中的人U87神经胶质瘤和MDA-MB-231乳腺肿瘤异种移植物导致显著的肿瘤生长延迟。我们的数据支持一种治疗方法的可行性,其中近红外光用于同时调制药物释放和诱导光热细胞杀伤。
Despite advances in controlled drug delivery, reliable methods for activatable, high-resolution control of drug release are needed. We hypothesized that the photothermal effect mediated by a near-infrared (NIR) laser and hollow gold nanospheres (HAuNS) could modulate the release of anticancer agents. We tested this hypothesis by developing biodegradable and biocompatible microspheres (1~15 µm) containing the antitumor drug paclitaxel (PTX) and HAuNS (~35 nm in diameter) displaying surface plasmon absorbance in the near-infrared (NIR) region. HAuNS-containing microspheres exhibited an NIR light-induced thermal effect similar to that of plain HAuNS. Rapid, repetitive PTX release from the PTX/HAuNS-containing microspheres was observed when microspheres were irradiated with NIR light (808 nm), whereas PTX release became insignificant when NIR light was switched off. The release of PTX from the microspheres could be readily controlled by NIR laser output power, duration of laser irradiation, treatment frequency, and the concentration of HAuNS embedded inside the microspheres. In vitro, cancer cells incubated with PTX/HAuNS-loaded microspheres and irradiated with NIR light displayed significantly greater cytotoxic effects than cells incubated with the microspheres alone or cells irradiated with NIR light alone, owing to NIR light-triggered drug release. Treatment of human U87 gliomas and MDA-MB-231 mammary tumor xenografts in nude mice with intratumoral injection of PTX/HAuNS-loaded microspheres followed by NIR irradiation resulted in significant tumor growth delay compared to tumors treated with HAuNS-loaded microspheres (no PTX) and NIR irradiation or with PTX/HAuNS-loaded microspheres alone. Our data support the feasibility of a therapeutic approach in which NIR light is used for simultaneous modulation of drug release and induction of photothermal cell killing.
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