NIR-Laser-Switched In Vivo Smart Nanocapsules for Synergic Photothermal and Chemotherapy of Tumors
NIR-Laser-Switched In Vivo Smart Nanocapsules for Synergic Photothermal and Chemotherapy of Tumors
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近红外激光开关体内智能纳米胶囊用于肿瘤的协同光热和化疗
DOI：
10.1002/adma.201502669
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发表时间：
2016-01-13
影响因子：
29.4
通讯作者：
Zhu, Meifang
中科院分区：
文献类型：
--
作者：
Meng, Zhouqi;Wei, Fang;Zhu, Meifang
Cu 2− xS [14] 和 WO 3− x [15] 基纳米制剂，用于体内癌细胞的光热消融。然而，应该指出的是，如果关闭 NIR 激光照射，NIR-PAT 将立即停止。为了进一步提高化疗或NIR-PAT的治疗效果，化疗和NIR-PAT的结合越来越受到人们的关注，并且已经研究了几种刺激响应纳米复合材料，包括PN@脂质体，[10b，16]PN@二氧化硅[17]和PN@聚合物，[18]在这些纳米复合材料中，PN@聚合物可能是最有前途的一种，因为 聚合物的刺激响应行为已被证明受到良好调节。例如，聚合物纳米凝胶的低临界溶液温度（LCST）可以在26至90℃之间变化。[19]目前，已经开发出多种PN@热响应聚合物，例如聚合物基PN@ PNIPAM，[20]碳基PN@ PNIPAM [21]和贵金属基PN@ PEG/NIPAM，[18]，它们可以在近红外激光照射下输送药物，极大地改善化疗/光热治疗。应该指出的是，对于所有这些刺激响应纳米复合材料，由于智能释放系统的缺乏或不足，近红外激光器的智能释放（关闭/打开）尚未得到很好的建立。因此，仍然有必要进一步开发智能纳米复合材料，可以通过离体近红外激光可控地关闭/开启，用于肿瘤的同步光热/化疗。在这里，我们描述了“智能”MEO 2MA@ MEO 2MA-co-OEGMA-CuS-DOX 复合材料（缩写为 G-CuS-DOX）的设计和制造，该复合材料由热敏 MEO 2MA@ MEO 2MA-co-OEGMA 纳米凝胶（缩写为 G）组成，LCST 为 42 C，作为纳米载体，CuS 纳米粒子作为光热材料 成分，以及阿霉素 (DOX) 作为抗癌药物（图 1a）。 G-CuS-DOX 纳米胶囊允许同时应用光热疗法和药物释放，可以通过离体近红外激光关闭/打开（图 2a）。随后，将纳米胶囊注入肿瘤并靠近癌细胞。在915纳米激光照射下，可有效杀灭癌细胞；对肿瘤生长和肝组织转移病灶均表现出明显的抑制作用，表明与单独光热治疗或化疗效果相比，光热/化疗协同治疗效果优异。 G-CuS-DOX 纳米胶囊的合成由四个步骤组成，如图 1a 所示。第一步是通过简单的聚合反应制备热敏 MEO 2MA 纳米凝胶（缩写为 M）（图 1a 中的步骤 1）。[18b] M 的平均流体动力学直径约为 90 nm（图 S1a，支持信息），LCST 约为 31 C（图 S1b，癌症对人类健康和生命构成巨大威胁。在癌症治疗中，化疗已被广泛应用 应用时，活性药物应以适当的浓度到达体内肿瘤，然后维持药物给药所需的时间以产生治疗效果。为了促进药物的输送和剂量控制，先进的刺激响应纳米载体最近受到了广泛的关注。刺激响应型纳米载体能够响应特定刺激来递送药物，无论是内源性变化（例如 pH、[1] 酶浓度和氧化还原梯度 [2]）或外源刺激（包括温度、[3] 磁场、[4] 超声强度、[5] 光、[6] 和电脉冲 [7]）。应该指出的是，随着...
Cu 2− xS [14] and WO 3− x [15] based nanoagents for the photothermal ablation of cancer cells in vivo. Nevertheless, it should be pointed out that NIR-PAT will cease immediately if the NIR laser irradiation is shut off. To further improve the therapeutic effects from chemotherapy or NIR-PAT, the combination of chemotherapy and NIR-PAT has attracted increasing attention, and several stimuli-responsive nanocomposites have been investigated, including PN@ liposome,[10b, 16] PN@ silica [17] and PN@ polymer,[18] Among these nanocomposites, PN@ polymer perhaps represents the most promising one, because the stimuli-responsive behavior of polymers has been demonstrated to be well regulated. For example, the low critical solution temperature (LCST) of polymer nanogels can be varied from 26 to 90 C.[19] Currently, several kinds of PN@ thermal-responsive polymers have been developed, such as polymer-based PN@ PNIPAM,[20] carbonbased PN@ PNIPAM [21] and noble-metal-based PN@ PEG/NIPAM,[18] which can deliver drugs under irradiation of an NIR laser, greatly improving chemo/photothermal therapy. It should be pointed out that for all these stimuli-responsive nanocomposites, the intelligent release (switching off/on) by NIR lasers is not yet well established due to the lack of or inadequacy of intelligent release systems. Therefore, it is still necessary to further develop smart nanocomposites that can be switched off/on controllably by an ex vivo NIR laser for simultaneous photothermal/chemotherapy of tumors. Here, we describe the design and fabrication of the “smart” MEO 2MA@ MEO 2MA-co-OEGMA-CuS-DOX composite (abbreviated as G-CuS-DOX), which consists of thermosensitive MEO 2MA@ MEO 2MA-co-OEGMA nanogels (abbreviated as G) with an LCST of 42 C, that serve as the nanocarriers, CuS nanoparticles as the photothermal component, and doxorubicin (DOX) as the anticancer drug (Figure 1a). G-CuS-DOX nanocapsules allow the application of photothermal therapy and drug release simultaneously, which can be switched off/on by an ex vivo NIR laser (Figure 2a). Subsequently, nanocapsules were injected into the tumor and close to cancer cells. Under irradiation with a 915-nm laser, cancer cells can be efficiently destroyed; both the tumor growth and metastasis lesions in liver tissue showed significant inhibition, indicating the excellent Synergic photothermal/chemotherapy effects compared to photothermal therapy or chemotherapy effect alone. The synthesis of G-CuS-DOX nanocapsules consisted of four steps, as demonstrated in Figure 1 a. The first step was to prepare a thermosensitive MEO 2MA nanogel (abbreviated as M) by a simple polymerization reaction (step 1 in Figure 1 a).[18b] M exhibits an average hydrodynamic diameter of≈ 90 nm (Figure S1a, Supporting Information) and an LCST of≈ 31 C (Figure S1b, Cancer poses a great threat to human health and life. Among cancer therapeutics, chemotherapy has been widely applied, in which the active drug should reach the tumor in vivo at the appropriate concentration, and administration of the drug should then be maintained for the required time to produce the therapeutic effect. To facilitate the delivery and dose control of drugs, advanced stimuli-responsive nanocarriers have recently received a great deal of attention. Stimuli-responsive nanocarriers are able to deliver drugs in response to specific stimuli, either endogenous variations (such as pH,[1] enzyme concentration, and redox gradients [2]) or exogenous stimuli (including temperature,[3] magnetic field,[4] ultrasound intensity,[5] light,[6] and electric pulses [7]). It should be noted that with …