The Effects of PLGA Nanoparticles Containing Different Growth Factors on Neural Stem Cell Differentiation and Their Transition Efficiency After Targeting With TRF

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-09-04 DOI:10.1111/cns.70576

Ayşegül Açıksarı, Yusufhan Yazır, Serap Mert, Zehra Seda Halbutoğulları, Sümeyye Narin, Gülçin Gacar

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Abstract

Aims

Nanoparticle-mediated drug delivery systems are being investigated for the controlled release of drugs to treat neurodegenerative diseases (ND). We aimed to investigate the effects of poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) containing different growth factors (GFs) on rat brain-derived neural stem cells (NSCs) in vitro differentiation, providing insights that may contribute to future approaches for treating Parkinson's disease.

Methods

Three different PLGA-NPs loaded with Brain-Derived Neurotrophic Factor (BDNF), Glial-Derived Neurotrophic Factor (GDNF), and Transforming Growth Factor beta 3 (TGF-β3) were developed and characterized in terms of size, zeta potential, encapsulation efficiency, and release profile. These NPs were used to differentiate NSCs into dopaminergic neurons in vitro. Additionally, the transition of transferrin (TRF)-conjugated PLGA-COOH-NPs across an in vitro blood–brain barrier (BBB) model was investigated.

Results

The average sizes of BDNF, GDNF, and TGF-ß3 loaded PLGA-NPs were measured to be 217.17 ± 1.37, 227.37 ± 5.39, and 220.57 ± 10.10 nm, respectively. Besides, SEM imaging revealed that the particles had a homogeneous size distribution and smooth surface morphology. Microtubule-associated protein 2 (Map2) and tyrosine hydroxylase (TH), two dopaminergic neuronal markers, were found in cells with neuron-like morphology that were produced through in vitro differentiation. The cellular uptake of PLGA-NPs loaded with Coumarin-6 was determined by using confocal imaging and flow cytometry. It was demonstrated that TRF-conjugated NPs were specifically targeted and taken up into NSCs in the in vitro BBB model.

Conclusion

It is concluded that BDNF-PLGA-NPs, GDNF-PLGA-NPs, and TGF-ß3-PLGA-NPs are promising brain drug delivery carriers for NSC inducers, which could be useful in developing strategies for Parkinson's disease management, particularly when targeted with TRF.

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含不同生长因子的PLGA纳米颗粒对TRF靶向后神经干细胞分化及转化效率的影响

目的研究纳米颗粒介导的药物递送系统，以控制药物释放治疗神经退行性疾病（ND）。我们旨在研究含有不同生长因子（GFs）的聚乳酸-羟基乙酸纳米颗粒（PLGA-NPs）对大鼠脑源性神经干细胞（NSCs）体外分化的影响，为未来治疗帕金森病的方法提供见解。方法制备了3种不同负载脑源性神经营养因子（BDNF）、胶质源性神经营养因子（GDNF）和转化生长因子β3 （TGF-β3）的PLGA-NPs，并对其大小、zeta电位、包封效率和释放特性进行了表征。这些NPs用于体外将NSCs分化为多巴胺能神经元。此外，我们还研究了转铁蛋白（TRF）偶联PLGA-COOH-NPs在体外血脑屏障（BBB）模型中的转移。结果BDNF、GDNF和TGF-ß3加载的PLGA-NPs平均大小分别为217.17±1.37、227.37±5.39和220.57±10.10 nm。扫描电镜（SEM）分析表明，颗粒尺寸分布均匀，表面形貌光滑。微管相关蛋白2 （Map2）和酪氨酸羟化酶（TH）是两种多巴胺能神经元标志物，在体外分化产生的神经元样形态细胞中发现。通过共聚焦成像和流式细胞术检测负载香豆素-6的PLGA-NPs的细胞摄取。结果表明，在体外血脑屏障模型中，trf结合的NPs被特异性靶向并被纳入NSCs。结论BDNF-PLGA-NPs、GDNF-PLGA-NPs和TGF-ß - 3- plga - nps是有希望的NSC诱导剂脑药物递送载体，可用于制定帕金森病的治疗策略，特别是当TRF靶向时。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.