Department of Experimental Diagnostic Imaging, Unit 59, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Small. 2010 May 7;6(9):1022-31. doi: 10.1002/smll.201000028.
Despite advances in controlled drug delivery, reliable methods for activatable, high-resolution control of drug release are needed. The hypothesis that the photothermal effect mediated by a near-infrared (NIR) laser and hollow gold nanospheres (HAuNSs) could modulate the release of anticancer agents is tested with biodegradable and biocompatible microspheres (1-15 microm) containing the antitumor drug paclitaxel (PTX) and HAuNSs (approximately 35 nm in diameter), which display surface plasmon absorbance in the NIR region. HAuNS-containing microspheres exhibit a NIR-induced thermal effect similar to that of plain HAuNSs. Rapid, repetitive PTX release from the PTX/HAuNS-containing microspheres is observed upon irradiation with NIR light (808 nm), whereas PTX release is insignificant when the NIR light is switched off. The release of PTX from the microspheres is readily controlled by the output power of the NIR laser, duration of irradiation, treatment frequency, and concentration of HAuNSs embedded inside the microspheres. In vitro, cancer cells incubated with PTX/HAuNS-loaded microspheres and irradiated with NIR light display 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 injections of PTX/HAuNS-loaded microspheres followed by NIR irradiation results 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. The 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.
尽管在控制药物释放方面取得了进展，但仍需要可靠的方法来实现可激活的、高分辨率的药物释放控制。本研究假设，近红外（NIR）激光和空心金纳米球（HAuNSs）介导的光热效应可以调节抗癌药物的释放，并通过含有抗癌药物紫杉醇（PTX）和 HAuNSs（直径约 35nm）的可生物降解和生物相容的微球（1-15μm）进行了测试，HAuNSs 在近红外区域显示出表面等离子体吸收。含有 HAuNS 的微球表现出与纯 HAuNS 相似的 NIR 诱导热效应。当用 NIR 光（808nm）照射时，观察到含有 PTX/HAuNS 的微球中迅速、重复地释放 PTX，而当关闭 NIR 光时，PTX 释放则不明显。微球中 HAuNS 的浓度、NIR 激光的输出功率、辐照时间、处理频率等因素都可以很容易地控制 PTX 的释放。体外实验结果表明，与单独孵育微球或单独用 NIR 光照射的细胞相比，用负载 PTX/HAuNS 的微球孵育并接受 NIR 光照射的癌细胞显示出显著更高的细胞毒性作用，这是由于 NIR 光触发的药物释放。用负载 PTX/HAuNS 的微球进行瘤内注射，然后用 NIR 光照射，治疗裸鼠中的人 U87 神经胶质瘤和 MDA-MB-231 乳腺癌异种移植瘤，与用负载 HAuNS 的微球（无 PTX）和 NIR 光照射或单独用负载 PTX/HAuNS 的微球治疗的肿瘤相比，肿瘤生长明显延迟。这些数据支持了一种治疗方法的可行性，即在该方法中，NIR 光用于同时调节药物释放和诱导光热细胞杀伤。
