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核壳型咪唑啉功能化介孔硅超顺磁杂化纳米粒子作为一种潜在的治疗诊断试剂用于铂(II)化合物的控制释放。

Core-Shell Imidazoline-Functionalized Mesoporous Silica Superparamagnetic Hybrid Nanoparticles as a Potential Theranostic Agent for Controlled Delivery of Platinum(II) Compound.

机构信息

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, Iran.

Center for Nanotechnology in Drug Delivery, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, Iran.

出版信息

Int J Nanomedicine. 2020 Apr 20;15:2617-2631. doi: 10.2147/IJN.S245135. eCollection 2020.

DOI:10.2147/IJN.S245135
PMID:32368044
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7182466/
Abstract

INTRODUCTION

As widely used chemotherapeutic agents, platinum compounds have several therapeutic challenges, such as drug resistance and adverse effects. Theranostic systems, macromolecular or colloidal therapeutics with companion diagnostics, not only address controlled drug delivery but also enable real-time monitoring of tumor sites.

METHODS

Synthesis of magnetic mesoporous silica nanoparticles (MMSNs) was performed for dual magnetic resonance imaging and drug delivery. MMSN surfaces were modified by imidazoline groups (MMSN-Imi) for cisplatin (Cis-Pt) conjugation via free N-termini to achieve well-controlled drug-release kinetics. Cis-Pt adsorption isotherms and drug-release profile at pH 5 and 7.4 were investigated using inductively coupled plasma atomic emission spectroscopy.

RESULTS

MMSN-Imi showed a specific surface area of 517.6 m g, mean pore diameter of 3.26 nm, and saturated magnetization of 53.63 emu/g. A relatively high r/r relaxivity value was obtained for MMSN-Imi. The nanoparticles provided high Cis-Pt loading with acceptable loading capacity (~30% w:w). Sustained release of Cis-Pt under acidic conditions led to specific inhibitory effects on the growth of human epithelial ovarian carcinoma cells, determined using MTT assays. Dual acridine orange-propidium iodide staining was investigated, confirming induction of apoptosis and necrotic cell death.

CONCLUSION

MMSN-Imi exhibited potential for applications in cancer chemotherapy and combined imaging.

摘要

简介

铂类化合物作为广泛应用的化疗药物，存在耐药性和不良反应等治疗挑战。治疗诊断系统，即具有伴随诊断的大分子或胶体治疗剂，不仅可以解决药物控释问题，还可以实现肿瘤部位的实时监测。

方法

合成了用于双重磁共振成像和药物递送的磁性介孔硅纳米粒子（MMSNs）。通过自由 N 末端将咪唑啉基团（MMSN-Imi）修饰到 MMSN 表面，用于顺铂（Cis-Pt）的共轭，以实现对药物释放动力学的良好控制。使用电感耦合等离子体原子发射光谱法研究了 Cis-Pt 吸附等温线和在 pH 5 和 7.4 下的药物释放曲线。

结果

MMSN-Imi 的比表面积为 517.6 m²/g，平均孔径为 3.26nm，饱和磁化强度为 53.63 emu/g。MMSN-Imi 的 r/r 弛豫率值相对较高。纳米粒子提供了高的 Cis-Pt 负载量，具有可接受的载药能力（约 30%w/w）。在酸性条件下持续释放 Cis-Pt 导致对人上皮性卵巢癌细胞生长的特异性抑制作用，通过 MTT 测定证实。进行了双重吖啶橙-碘化丙啶染色，证实了诱导细胞凋亡和坏死性细胞死亡。

结论

MMSN-Imi 具有应用于癌症化学治疗和联合成像的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec65/7182466/cdab7fda7d46/IJN-15-2617-g0009.jpg
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