用槲皮素递送超顺磁性聚合物胶束到肝细胞癌细胞。

StephenW

J Pharm Sci. 2018 Aug 16. pii: S0022-3549(18)30507-0. doi: 10.1016/j.xphs.2018.08.008. [Epub ahead of print]
Delivery of Superparamagnetic Polymeric Micelles Loaded with Quercetin to Hepatocellular Carcinoma Cells.
Srisa-Nga K1, Mankhetkorn S2, Okonogi S3, Khonkarn R4.
Author information

1
    Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand; Graduate School, Chiang Mai University, Thailand.
2
    Laboratory of Physical Chemistry, Molecular and Cellular Biology, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
3
    Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand; Research Center of Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand.
4
    Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand; Research Center of Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: [email protected].

Abstract

The aim of this study was to develop co-encapsulation of quercetin (QCT) and superparamagnetic iron oxide nanoparticles (SPIONs) into methoxy-poly(ethylene glycol)-b-oligo(ɛ-caprolactone), mPEG750-b-OCL-Bz micelles (QCT-SPIONs-loaded micelles) for inhibition of hepatitis B virus-transfected hepatocellular carcinoma (HepG2.2.15) cell growth. QCT-SPIONs-loaded micelles were prepared using film hydration method. They were spherical in shape with average size of 22-55 nm. The best QCT-SPIONs-loaded micelles showed entrapment efficiency and loading capacity of QCT at 70% and 3.5%, respectively and of SPIONs at 15% and 0.8%, respectively. Transverse (T2) relaxivity of SPIONs was 137 mM-1s-1. SPIONs clusters present inside the core of QCT-SPIONs-loaded micelles increased T2 relaxivity value (246 mM-1s-1) indicating the good magnetic resonance imaging (MRI) sensitivity of QCT-SPIONs-loaded micelles in comparison with SPIONs. QCT-SPIONs-loaded micelles could be taken up by HepG2.2.15 cells and showed higher cytotoxicity than QCT. Further, these cells were arrested by QCT-SPIONs-loaded micelles at the G0/G1 phase of cell cycle. QCT-SPIONs-loaded micelles accumulated in vicinity of NdFeB magnetic disc, resulting in the potent inhibition of cancer cell growth at the strong magnetic field strength. In conclusion, mPEG750-b-OCL-Bz micelles are a promising multi-functional vehicle for co-delivery of QCT and SPIONs for disease monitoring and therapies of hepatocellular carcinoma.
KEYWORDS:

magnetic nanocarrier; polymeric micelles; quercetin; superparamagnetic iron oxide nanoparticles

PMID:
    30121312
DOI:
    10.1016/j.xphs.2018.08.008

StephenW

J Pharm Sci。 2018年8月16日.pii：S0022-3549（18）30507-0。 doi：10.1016 / j.xphs.2018.08.008。 [提前打印]
用槲皮素递送超顺磁性聚合物胶束到肝细胞癌细胞。
Srisa-Nga K1，Mankhetkorn S2，Okonogi S3，Khonkarn R4。
作者信息

1
    泰国清迈清迈大学药学院药学系;泰国清迈大学研究生院。
2
    泰国清迈清迈大学相关医学院放射技术系物理化学，分子与细胞生物学实验室。
3
    泰国清迈清迈大学药学院药学系;清迈大学药物纳米技术研究中心，泰国清迈50200。
4
    泰国清迈清迈大学药学院药学系;清迈大学药物纳米技术研究中心，泰国清迈50200。电子地址：[email protected]。

抽象

本研究的目的是开发槲皮素（QCT）和超顺磁性氧化铁纳米粒子（SPIONs）共包封成甲氧基 - 聚（乙二醇）-b-低聚（ε-己内酯），mPEG750-b-OCL-Bz胶束。 （QCT-SPIONs加载的胶束）用于抑制乙型肝炎病毒转染的肝细胞癌（HepG2.2.15）细胞生长。使用膜水合方法制备负载QCT-SPION的胶束。它们是球形的，平均尺寸为22-55nm。最好的QCT-SPIONs胶束显示QCT的包封率和负载能力分别为70％和3.5％，SPIONs的负载能力分别为15％和0.8％。 SPION的横向（T2）弛豫率为137mM-1s-1。存在于负载QCT-SPION的胶束核心内的SPION簇增加了T2弛豫值（246mM-1s-1），表明与SPION相比，负载QCT-SPION的胶束具有良好的磁共振成像（MRI）灵敏度。携带QCT-SPIONs的胶束可被HepG2.2.15细胞摄取并显示出比QCT更高的细胞毒性。此外，这些细胞在细胞周期的G0 / G1期被装载QCT-SPIONs的胶束阻止。装载QCT-SPIONs的胶束累积在NdFeB磁盘附近，导致在强磁场强度下有效抑制癌细胞生长。总之，mPEG750-b-OCL-Bz胶束是一种有前途的多功能载体，用于共同递送QCT和SPION用于肝细胞癌的疾病监测和治疗。
关键词：

磁性纳米载体;聚合物胶束;槲皮素;超顺磁性氧化铁纳米粒子

结论：
    30121312
DOI：
    10.1016 / j.xphs.2018.08.008