化学
两亲性
生物物理学
纳米颗粒
药物输送
活性氧
神经干细胞
分子
组合化学
纳米技术
生物化学
有机化学
干细胞
细胞生物学
共聚物
聚合物
材料科学
生物
作者
Li Yan,Yanhui Li,Wei‐Qiang Ji,Zhiguo Lü,Linying Liu,Yuanjie Shi,Guanghui Ma,Xin Zhang
摘要
Due to the vast differences in chemical properties among small molecule drugs, nucleotide drugs, and superparamagnetic iron oxide nanocubes (SPIONs), such as charge and hydrophobicity, entrapment of these within a single carrier for traceable synergistic therapy has been proven difficult. Herein, we synthesize positively charged polyprodrug amphiphiles. The hydrophobic polyprodrug unit of the amphiphiles is positively charged, which can simultaneously load hydrophobic SPIONs and absorb negative let-7b antisense oligonucleotide to construct traceable co-delivery nanoparticles (NPs). This characteristic avoids the use of inert materials and enhances drug loading of the traceable NPs. The traceable NPs can achieve controlled release of drugs to reduce the differentiation of exogenous neural stem cells (NSCs) and enhance their secretion of brain-derived neurotrophic factor (BDNF) synergistically. Exogenous NSCs treated with the NPs significantly rescue the memory deficits in 2xTg-AD mice. In addition, the transplantation site and migration of exogenous NSCs can be traced using the SPIONs with high r2 value for magnetic resonance imaging. Therefore, traceable NPs self-assembled from the positively charged polyprodrug amphiphiles may have the potential to open up a new avenue for treatment of Alzheimer’s disease (AD), as well as other neurodegenerative disorders.
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