Stimuli-Responsive, Plasmonic Nanogel for Dual Delivery of Curcumin and Photothermal Therapy for Cancer Treatment.
Stimuli-Responsive, Plasmonic Nanogel for Dual Delivery of Curcumin and Photothermal Therapy for Cancer Treatment.
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DOI：
10.3389/fchem.2020.602941
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发表时间：
2020
影响因子：
5.5
通讯作者：
Rosenholm JM
中科院分区：
文献类型：
--
作者：
Howaili F;Özliseli E;Küçüktürkmen B;Razavi SM;Sadeghizadeh M;Rosenholm JM
纳米凝胶（Ng）是基于交联聚合物的水凝胶纳米颗粒，由于其上级性质，包括高载药量、低毒性和刺激响应性，被认为是下一代药物递送系统。在本研究中，通过在化学交联剂的存在下将聚（N-异丙基丙烯酰胺）（PNIPAM）接枝到壳聚糖（CS）上来合成双重温度-pH-响应等离子体纳米凝胶（AuNP@Ng），以作为药物载体系统。纳米凝胶进一步与金纳米颗粒（AuNP）结合，以提供同时的药物递送和光热治疗（PTT）。姜黄素（Cur）的低水溶性和低生物利用度是姜黄素有效用于抗癌治疗的最大障碍，并且这些障碍可以通过利用有效的递送系统来克服。因此，选择姜黄素作为模型药物负载到纳米凝胶中以增强抗癌效率，并且进一步地，通过配制的AuNP@Ng的PTT增强其治疗效率。进行基于CS和PNIPAM的Ng的彻底表征以确认成功的合成。此外，制备的纳米粒子的光热性能和溶胀比进行了评价。通过透射电子显微镜（TEM）、扫描电子显微镜（SEM）和X射线能谱（EDX）对纳米凝胶的形貌和尺寸进行了表征。纳米凝胶被发现具有约167 nm的流体动力学尺寸，并表现出姜黄素的持续释放长达72 h，具有双重热pH响应性药物释放行为，如在不同温度和pH条件下检查的。在MDA-MB-231人乳腺癌和非致瘤性MCF 10A细胞系上评估等离子体纳米凝胶的细胞相容性，并且发现表明纳米凝胶制剂是细胞相容的。纳米颗粒摄取研究显示，与非致瘤细胞相比，纳米颗粒在癌细胞中具有高内化，并且共聚焦显微镜进一步证明AuNP@Ng通过内体途径内化到MDA-MB-231癌细胞中。体外细胞毒性研究显示姜黄素负载AuNP@Ng/Cur的剂量依赖性和时间依赖性药物递送。此外，所开发的纳米颗粒在体外用近红外（NIR）激光（808 nm）照射时显示出改善的化疗疗效。这项工作揭示了负载姜黄素的合成等离子体纳米凝胶（AuNP@Ng/Cur）可以充当刺激响应性纳米载体，具有双重治疗的潜力，即，疏水性药物的递送和光热疗法。
Nanogels (Ng) are crosslinked polymer-based hydrogel nanoparticles considered to be next-generation drug delivery systems due to their superior properties, including high drug loading capacity, low toxicity, and stimuli responsiveness. In this study, dually thermo-pH-responsive plasmonic nanogel (AuNP@Ng) was synthesized by grafting poly (N-isopropyl acrylamide) (PNIPAM) to chitosan (CS) in the presence of a chemical crosslinker to serve as a drug carrier system. The nanogel was further incorporated with gold nanoparticles (AuNP) to provide simultaneous drug delivery and photothermal therapy (PTT). Curcumin's (Cur) low water solubility and low bioavailability are the biggest obstacles to effective use of curcumin for anticancer therapy, and these obstacles can be overcome by utilizing an efficient delivery system. Therefore, curcumin was chosen as a model drug to be loaded into the nanogel for enhancing the anticancer efficiency, and further, its therapeutic efficiency was enhanced by PTT of the formulated AuNP@Ng. Thorough characterization of Ng based on CS and PNIPAM was conducted to confirm successful synthesis. Furthermore, photothermal properties and swelling ratio of fabricated nanoparticles were evaluated. Morphology and size measurements of nanogel were determined by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Nanogel was found to have a hydrodynamic size of ~167 nm and exhibited sustained release of curcumin up to 72 h with dual thermo-pH responsive drug release behavior, as examined under different temperature and pH conditions. Cytocompatibility of plasmonic nanogel was evaluated on MDA-MB-231 human breast cancer and non-tumorigenic MCF 10A cell lines, and the findings indicated the nanogel formulation to be cytocompatible. Nanoparticle uptake studies showed high internalization of nanoparticles in cancer cells when compared with non-tumorigenic cells and confocal microscopy further demonstrated that AuNP@Ng were internalized into the MDA-MB-231 cancer cells via endosomal route. In vitro cytotoxicity studies revealed dose-dependent and time-dependent drug delivery of curcumin loaded AuNP@Ng/Cur. Furthermore, the developed nanoparticles showed an improved chemotherapy efficacy when irradiated with near-infrared (NIR) laser (808 nm) in vitro. This work revealed that synthesized plasmonic nanogel loaded with curcumin (AuNP@Ng/Cur) can act as stimuli-responsive nanocarriers, having potential for dual therapy i.e., delivery of hydrophobic drug and photothermal therapy.
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