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用于巨噬细胞靶向递送纳米颗粒的葡聚糖颗粒。

Glucan particles for macrophage targeted delivery of nanoparticles.

作者信息

Soto Ernesto R, Caras Abaigeal C, Kut Lindsey C, Castle Melissa K, Ostroff Gary R

机构信息

Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.

出版信息

J Drug Deliv. 2012;2012:143524. doi: 10.1155/2012/143524. Epub 2011 Oct 13.

Abstract

Glucan particles (GPs) are hollow, porous 2-4 μm microspheres derived from the cell walls of Baker's yeast (Saccharomyces cerevisiae). The 1,3-β-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. GPs have been used for macrophage-targeted delivery of soluble payloads (DNA, siRNA, protein, and small molecules) encapsulated inside the hollow GPs via core polyplex and layer-by-layer (LbL) synthetic strategies. In this communication, we report the incorporation of nanoparticles as cores inside GPs (GP-NP) or electrostatically bound to the surface of chemically derivatized GPs (NP-GP). GP nanoparticle formulations benefit from the drug encapsulation properties of NPs and the macrophage-targeting properties of GPs. GP nanoparticle formulations were synthesized using fluorescent anionic polystyrene nanoparticles allowing visualization and quantitation of NP binding and encapsulation. Mesoporous silica nanoparticles (MSNs) containing the chemotherapeutic doxorubicin (Dox) were bound to cationic GPs. Dox-MSN-GPs efficiently delivered Dox into GP phagocytic cells resulting in enhanced Dox-mediated growth arrest.

摘要

葡聚糖颗粒(GPs)是源自面包酵母(酿酒酵母)细胞壁的中空、多孔的2-4微米微球。1,3-β-葡聚糖外壳可被表达β-葡聚糖受体的吞噬细胞通过受体介导摄取。GPs已被用于通过核心复合物和逐层(LbL)合成策略,将封装在中空GPs内部的可溶性负载(DNA、siRNA、蛋白质和小分子)靶向递送至巨噬细胞。在本通讯中,我们报告了将纳米颗粒作为核心掺入GPs内部(GP-NP)或静电结合到化学衍生GPs表面(NP-GP)的情况。GP纳米颗粒制剂受益于NP的药物封装特性和GPs的巨噬细胞靶向特性。使用荧光阴离子聚苯乙烯纳米颗粒合成了GP纳米颗粒制剂,从而能够对NP的结合和封装进行可视化和定量分析。含有化疗药物阿霉素(Dox)的介孔二氧化硅纳米颗粒(MSNs)与阳离子GPs结合。Dox-MSN-GPs能够有效地将Dox递送至GP吞噬细胞,从而增强Dox介导的生长停滞。

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