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温敏聚合物门控和超顺磁性纳米颗粒嵌入的中空介孔硅纳米粒子作为智能多功能纳米载体,用于阿霉素的靶向和控制释放。

Thermoresponsive polymer gated and superparamagnetic nanoparticle embedded hollow mesoporous silica nanoparticles as smart multifunctional nanocarrier for targeted and controlled delivery of doxorubicin.

机构信息

School of Engineering Sciences and Technology, University of Hyderabad, Hyderabad 500046, India.

出版信息

Nanotechnology. 2020 Nov 6;31(45):455604. doi: 10.1088/1361-6528/ab8b0e. Epub 2020 Apr 20.

Abstract

The design and development of drug-delivery nanocarriers with high loading capacity, excellent biocompatibility, targeting ability and controllability have been the ultimate goal of the biomedical research community. In this work, we have reported the synthesis and characterization of novel and smart thermoresponsive polymer coated and FeO embedded hollow mesoporous silica (HmSiO) based multifunctional superparamagnetic nanocarriers for the delivery of doxorubicin (Dox) for cancer treatment. P(NIPAM-MAm) coated and FeO nanoparticle (NP) embedded hollow mesoporous silica nanocomposite (HmSiO-F-P(NIPAM-MAm)) was prepared by the in situ polymerization of NIPAM and MAm monomers on the surface of hollow mesoporous silica NPs (HmSiO) in the presence of FeO NPs, oxidizer and crosslinker. TEM analysis showed nearly spherical morphology of HmSiO-F-P(NIPAM-MAm) nanocarrier with a diameter in the range of 100-300 nm. The coating of P(NIPAM-MAm) layer and embedding of FeO NPs on the surface of the HmSiO NPs was revealed by HRTEM analysis. XRD and FTIR analysis also confirmed the presence of P(NIPAM-MAm) shells and FeO NPs on hollow mesoporous silica NPs. VSM analysis suggested the superparamagnetic nature of HmSiO-F-P(NIPAM-MAm) nanocarrier. DSC analysis of HmSiO-F-P(NIPAM-MAm) nanocarrier showed a phase transition at the temperature of ∼38 °C. The prepared HmSiO-F-P(NIPAM-MAm) nanocarrier was investigated for its suitability for drug-delivery application using doxorubicin as the model drug by an in vitro method. The encapsulation efficiency and encapsulation capacity were found to be 95% and 6.8%, respectively. HmSiO-F-P(NIPAM-MAm)-Dox has shown a pH and temperature-dependent Dox release profile. A relatively faster release of Dox from the nanocarrier was observed at temperature above the lower critical solution temperature (LCST) than below the LCST. HmSiO-F-P(NIPAM-MAm) nanocarrier was found to be biocompatible in nature. In vitro cytotoxicity studies against Hela cells suggested that the HmSiO-F-P(NIPAM-MAm)-Dox nanocomposite nanocarrier has good anticancer activity. In vitro cellular uptake study of HmSiO-F-P(NIPAM-MAm)-Dox nanocomposite nanocarrier demonstrated its good internalisation ability into Hela cells. Thus, the prepared nanocomposites show potential as nanocarrier for targeted and controlled drug delivery for cancer treatment.

摘要

新型智能温敏聚合物包覆的 FeO 嵌入中空介孔硅(HmSiO)多功能超顺磁纳米载体的设计与开发,具有高载药量、良好的生物相容性、靶向能力和可控性,一直是生物医学研究领域的最终目标。在这项工作中,我们报道了一种新型智能温敏聚合物包覆的 FeO 嵌入中空介孔硅(HmSiO)多功能超顺磁纳米载体的合成与表征,用于输送阿霉素(Dox)进行癌症治疗。通过在中空介孔硅纳米粒子(HmSiO)表面原位聚合 NIPAM 和 MAm 单体,在存在 FeO 纳米粒子、氧化剂和交联剂的情况下,制备了 P(NIPAM-MAm)包覆和 FeO 纳米粒子(NP)嵌入的中空介孔硅纳米复合材料(HmSiO-F-P(NIPAM-MAm))。TEM 分析表明,HmSiO-F-P(NIPAM-MAm)纳米载体具有近球形形态,直径在 100-300nm 范围内。通过高分辨透射电子显微镜(HRTEM)分析证实了 P(NIPAM-MAm)层的包覆和 FeO NPs 在 HmSiO NPs 表面的嵌入。XRD 和 FTIR 分析也证实了 P(NIPAM-MAm)壳和 FeO NPs 存在于中空介孔硅 NPs 上。振动样品磁强计(VSM)分析表明,HmSiO-F-P(NIPAM-MAm)纳米载体具有超顺磁性。HmSiO-F-P(NIPAM-MAm)纳米载体的差示扫描量热分析(DSC)表明,在约 38°C 时发生相转变。通过体外法以阿霉素(DOX)为模型药物,对 HmSiO-F-P(NIPAM-MAm)纳米载体的药物输送适用性进行了研究。包封效率和包封率分别为 95%和 6.8%。HmSiO-F-P(NIPAM-MAm)-Dox 表现出 pH 值和温度依赖性 DOX 释放谱。在低于低临界溶液温度(LCST)的温度下,与低于 LCST 时相比,纳米载体中 DOX 的释放速度相对较快。HmSiO-F-P(NIPAM-MAm)纳米载体具有良好的生物相容性。对 Hela 细胞的体外细胞毒性研究表明,HmSiO-F-P(NIPAM-MAm)-Dox 纳米复合材料纳米载体具有良好的抗癌活性。HmSiO-F-P(NIPAM-MAm)-Dox 纳米复合材料纳米载体的体外细胞摄取研究表明,其具有良好的内化能力进入 Hela 细胞。因此,所制备的纳米复合材料有望成为用于癌症治疗的靶向和控制药物输送的纳米载体。

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