Preliminary delivery efficiency prediction of nanotherapeutics into crucial cell populations in bone marrow niche

IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Huijuan Chen , Anzhi Hu , Mengdi Xiao , Shiyi Hong , Jing Liang , Quanlong Zhang , Yang Xiong , Mancang Gu , Chaofeng Mu
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Abstract

Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches. Precise regulation of these cell types can remodel niches and develop new therapeutics. Multiple nanocarriers have been developed to transport drugs into the bone marrow selectively. However, the delivery efficiency of these nanotherapeutics into crucial niche cells is still unknown, and there is no method available for predicting delivery efficiency in these cell types. Here, we constructed a three-dimensional bone marrow niche composed of three crucial cell populations: endothelial cells (ECs), mesenchymal stromal cells (MSCs), and osteoblasts (OBs). Mimetic niches were used to detect the cellular uptake of three typical drug nanocarriers into ECs/MSCs/OBs in vitro. Less than 5% of nanocarriers were taken up by three stromal cell types, and most of them were located in the extracellular matrix. Delivery efficiency in sinusoidal ECs, arteriole ECs, MSCs, and OBs in vivo was analyzed. The correlation analysis showed that the cellular uptake of three nanocarriers in crucial cell types in vitro is positively linear correlated with its delivery efficiency in vivo. The delivery efficiency into MSCs was remarkably higher than that into ECs and OBs, no matter what kind of nanocarrier. The overall efficiency into sinusoidal ECs was greatly lower than that into arteriole ECs. All nanocarriers were hard to be delivered into OBs (<1%). Our findings revealed that cell tropisms of nanocarriers with different compositions and ligand attachments in vivo could be predicted via detecting their cellular uptake in bone marrow niches in vitro. This study provided the methodology for niche-directed nanotherapeutics development.

Abstract Image

纳米治疗药物进入骨髓生态位关键细胞群的初步递送效率预测
几个关键的基质细胞群调节造血和骨髓龛中的恶性疾病。对这些细胞类型的精确调控可以重塑生态位并开发新的治疗方法。多种纳米载体已经被开发出来,可以选择性地将药物运送到骨髓中。然而,这些纳米治疗药物在关键生态位细胞中的递送效率仍然未知,并且没有可用的方法来预测这些细胞类型的递送效率。在这里,我们构建了一个由三个关键细胞群组成的三维骨髓生态位:内皮细胞(ECs)、间充质基质细胞(MSCs)和成骨细胞(OBs)。采用模拟壁龛法检测三种典型药物纳米载体在体外对ECs/MSCs/OBs的细胞摄取。三种基质细胞占纳米载体的比例均不到5%,且大部分位于细胞外基质中。在体内分析正弦内皮细胞、小动脉内皮细胞、间充质干细胞和OBs的传递效率。相关分析表明,三种纳米载体在体外对关键细胞类型的细胞摄取与其在体内的递送效率呈线性正相关。无论何种纳米载体,MSCs的递送效率均显著高于ECs和OBs。进入正弦波内皮细胞的总效率远低于进入小动脉内皮细胞的总效率。所有纳米载体都难以进入OBs (<1%)。我们的研究结果表明,不同组成和配体附着的纳米载体在体内的细胞趋向性可以通过检测其在体外骨髓壁龛中的细胞摄取来预测。本研究为小生境定向纳米疗法的开发提供了方法学依据。
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来源期刊
Asian Journal of Pharmaceutical Sciences
Asian Journal of Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
18.30
自引率
2.90%
发文量
11
审稿时长
14 days
期刊介绍: The Asian Journal of Pharmaceutical Sciences (AJPS) serves as the official journal of the Asian Federation for Pharmaceutical Sciences (AFPS). Recognized by the Science Citation Index Expanded (SCIE), AJPS offers a platform for the reporting of advancements, production methodologies, technologies, initiatives, and the practical application of scientific knowledge in the field of pharmaceutics. The journal covers a wide range of topics including but not limited to controlled drug release systems, drug targeting, physical pharmacy, pharmacodynamics, pharmacokinetics, pharmacogenomics, biopharmaceutics, drug and prodrug design, pharmaceutical analysis, drug stability, quality control, pharmaceutical engineering, and material sciences.
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