School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China; Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, 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.
Acta Biomater. 2015 Apr;17:201-9. doi: 10.1016/j.actbio.2015.01.026. Epub 2015 Jan 30.
Stimuli-responsive drug delivery systems have been developed to enhance the tumor-targeting drug transportation and minimize the severe side effects along with the chemotherapy. In this study, a near-infrared (NIR) light triggered drug delivery system was developed based on the amphiphilic chitosan derivative-coated single-wall carbon nanotubes (CNT) encapsulated in the thermo/pH sensitive nanogel (CS/PNIPAAm@CNT). The PEG diacrylate (Mw = 250 Da) was applied in the present work to tune the nanoparticles with the phase transition temperature at ∼ 38 °C, which was an attempt to match the prerequisite for the in vivo applications. Owing to the π-π stacking, hydrophobic interaction and the opportunity of Schiff-base formation between chitosan and doxorubicin (DOX), the nanoparticles possessed a relative high drug loading capacity (∼ 43%). The DOX loaded CS/PNIPAAm@CNT released DOX faster at 40 °C than at 25 °C, meanwhile faster at pH 5.0 in comparison with that at pH 7.4. Moreover, the rapid and repetitive release of DOX was observed when the DOX-loaded CS/PNIPAAm@CNT was irradiated under NIR light. Furthermore, DOX-loaded CS/PNIPAAm@CNT upon NIR irradiation showed significantly greater cytotoxicity in HeLa cells owing to NIR-triggered increase in temperature and enhanced DOX release. Confocal laser scanning microscopy (CLSM) was utilized to demonstrate the enhanced cell uptake of the as prepared nanoparticles and the faster drug release under the NIR irradiation and lower pH. All the results suggest that multifunctional DOX-loaded CS/PNIPAAm@CNT nanocomposite is a promising therapeutic nanocarrier for intracellular drug delivery with great potential for targeted cancer therapy.
刺激响应型药物递送系统已被开发出来,以增强肿瘤靶向药物输送,并最大限度地减少化疗的严重副作用。在本研究中,基于两亲性壳聚糖衍生物包覆的单壁碳纳米管(CNT)封装在热/ pH 敏感纳米凝胶(CS/PNIPAAm@CNT)中,开发了近红外(NIR)光触发药物递送系统。在本工作中应用了聚乙二醇二丙烯酸酯(Mw = 250 Da),以将纳米颗粒的相变温度调谐至约 38°C,这是尝试与体内应用的前提条件相匹配。由于壳聚糖和阿霉素(DOX)之间的π-π堆积、疏水相互作用和席夫碱形成的机会,纳米颗粒具有相对较高的药物负载能力(约 43%)。负载 DOX 的 CS/PNIPAAm@CNT 在 40°C 下比在 25°C 下更快地释放 DOX,同时在 pH 5.0 下比在 pH 7.4 下更快地释放 DOX。此外,当负载 DOX 的 CS/PNIPAAm@CNT 在 NIR 光下照射时,观察到 DOX 的快速和重复释放。此外,由于 NIR 触发的温度升高和增强的 DOX 释放,负载 DOX 的 CS/PNIPAAm@CNT 在 NIR 照射下对 HeLa 细胞表现出显著更高的细胞毒性。共聚焦激光扫描显微镜(CLSM)用于证明所制备的纳米颗粒的增强细胞摄取以及在 NIR 照射和较低 pH 下更快的药物释放。所有结果表明,多功能负载 DOX 的 CS/PNIPAAm@CNT 纳米复合材料是一种有前途的用于细胞内药物递送的治疗性纳米载体,具有用于靶向癌症治疗的巨大潜力。
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