INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
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IF 8.025
Yuying Xu,Minting Liang,Jintao Huang,Yapei Fan,Haiyue Long,Qunjie Chen,Zhe Ren,Chaoxi Wu,Yifei Wang
Single helical β -glucan is a one-dimensional host that can form a hybrid helix with DNAs/RNAs as delivery systems. However, unmodified β -glucan has a gelling tendency and a single helical conformation is challenging to obtain. Therefore, in this study, we developed a β -glucan formyl derivative with stable single helical conformation and no gelling tendency. Circular dichroism studies found that the formyl- β -glucan could form a hybrid helix with DNA CpG-poly(dA). The hybrid helix delivery system showed improved activation on antigen-presenting cells, thereby upregulating the mRNA and protein levels of inflammatory factors, and had an immune-enhancing effect on ovalbumin (OVA) immunized mice. These results indicate that formyl- β -glucan can be developed as a non-cationic supramolecular DNA delivery platform with low toxicity and high efficiency.
研究领域:
生物技术
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免疫学
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药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Qingfei Sun,Yueyue Gui,Chong Fan,Jiaxiong Li,Xiaomeng Tan,Chao Li,Jin Qiu,Jiehua Ma
Macrophages use pattern recognition receptors (PRRs) to recognize, capture, and phagocytize pathogens. Recreating artificial systems to mimic such receptors for manipulating macrophage predation is both scientifically exciting and technologically relevant to anti-infection. Nevertheless, fabricating synthetic PRR-mimicking receptors with a predictable and stable structure remains a challenge. Herein, we use circular aptamers as building blocks to create artificial DNA receptors (ADRs) that mimic the function of PRRs. After modification of ADRs on macrophages, they can stably recognize specific pathogens and promote the phagocytosis of macrophages, akin to natural PRRs. As dynamic structures, these ADRs can be flexibly activated or inactivated by external DNA molecules, akin to protein receptors responding to small-molecule ligands. Owing to the programmability of the DNA reaction, Boolean logic operations can be introduced to logically manipulate the predation behavior of macrophages, exhibiting the characteristics of artificial receptors. Furthermore, ADRs can be integrated with other functional DNA motifs, e.g., CpG DNA, to enhance the activation and antibacterial capacity of macrophages with higher efficiency. Overall, we believe that this artificial receptor not only broadens the application of DNA nanotechnology in cell biology but also contributes to ongoing efforts to remodel the innate immune system for fighting infection in consideration of the growing emergence of multidrug-resistant bacteria.
研究领域:
细胞生物学
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纳米技术
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
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2023
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IF 9.7
Yizhong Peng,Xuanzuo Chen,Zilong Rao,Wei Wu,Huiyin Zuo,Kaibin Chen,Kanglu Li,Hui Lin,Sheng Liu,Yan Xiao,BaiChuan Wang,Daping Quan,Xiangcheng Qing,Ying Bai,Zengwu Shao
Chronic low back pain mainly attributed to intervertebral disc (IVD) degeneration. Endogenous damage-associated molecular patterns (DAMPs) in the injured IVD, particularly mitochondria-derived nucleic acid molecules (CpG DNA), play a primary role in the inflammatory responses in macrophages. M1-type macrophages form a chronic inflammatory microenvironment by releasing pro-inflammatory factors and nerve growth factor (NGF) that induce nerve growth into the inner annulus fibrosus, resulting in persistent hyperalgesia. We fabricated an amphiphilic polycarbonate that naturally forms cationic nanoparticles (cNP) in aqueous solutions, with the hydrophobic core loaded with TrkA-IN-1, an antagonist against the NGF receptor (TrkA). The drug delivery nanoparticles were denoted as TI-cNP. TrkA-IN-1 and TI-cNP were added to the decellularized annulus fibrosus matrix (DAF) hydrogel to form hybrid hydrogels, denoted as TI-DAF and TI-cNP-DAF, respectively. As a result, TrkA-IN-1 showed a delayed release profile both in TI-DAF and TI-cNP-DAF. Each mole of cNP could bind approximately 3 mol of CpG DNA to inhibit inflammation. cNP-DAF and TI-cNP-DAF significantly inhibited the M1 phenotype induced by CpG DNA. TI-DAF and TI-cNP-DAF reduced neurite branching and axon length, and inhibited the expression of neurogenic mediators (CGRP and substance P) in the presence of NGF. Besides, TI-cNP-DAF relieved mechanical hyperalgesia, reduced CGRP and substance P expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat disc herniation model. Summarily, TI-cNP-DAF, a novel composite IVD hydrogel, efficiently mediated the inflammatory environment, inhibited nerve ingrowth and sensitization, and could be clinically applied for treating discogenic pain. Statement of Significance : Discogenic lower back pain, related to intervertebral disc degeneration (IDD), imposes a tremendous health and economic burden globally. M1-type macrophages release pro-inflammatory factors and nerve growth factor (NGF) that induce nerve growth into the inner annulus fibrosus, resulting in persistent hyperalgesia and discogenic pain. Reconstructing matrix integrity and modulating the inflammatory microenvironment are promising strategies for preventing the ingrowth and activation of neurites. The TI-cNP-DAF hydrogel recovers tissue integrity, alleviates inflammation, and delivers the TrkA antagonist to inhibit the activity of NGF, thus restraining hyperinnervation and nociceptive input. Due to its simple production process, injectability, and acellular strategy, the hydrogel is operable and holds great potential for treating discogenic lower back pain.
研究领域:
生物医学工程
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神经科学
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疼痛管理
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组织工程
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）