A novel nano delivery system targeting different stages of osteoclasts

Zhang, Bosong; Zhao, Juzhi; Yan, Hongji; Zhao, Yufang; Tian, Hui; Cao, Wang Fang; Wang, Ruiqi; Jin, Jiaming; Chen, Yue; Yang, Chaofan; Li, Chunfeng; Jiao, Yanwen; Zheng, Kaipeng; Zhu, Fuxing; Tian, Weiming

doi:10.1039/d2bm00076h

Cited by 9 publications

(5 citation statements)

References 47 publications

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“…As a result, protecting polyphenols in vivo and delivery to the nervous system have been challenging and remain to be addressed. Our previous studies have demonstrated that hyaluronic acid (HA) has good neuroinflammation resistance, 20 as well as suitable biocompatibility in many biomedical applications 21–27 . Studies have shown that mitochondrial abnormalities are the leading cause of ROS accumulation in the nervous system 28 .…”

Section: Introductionmentioning

confidence: 99%

“…Our previous studies have demonstrated that hyaluronic acid (HA) has good neuroinflammation resistance, 20 as well as suitable biocompatibility in many biomedical applications. 21 , 22 , 23 , 24 , 25 , 26 , 27 Studies have shown that mitochondrial abnormalities are the leading cause of ROS accumulation in the nervous system. 28 Further, our recent studies found that HA can reduce ROS and restore neural damage by protecting the mitochondria.…”

Section: Introductionmentioning

confidence: 99%

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Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease

Zhang

Zhao

Guo

et al. 2022

Bioengineering & Transla Med

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Prevention and early intervention are the current focus of treatment for Alzheimer's disease (AD). An increase in reactive oxygen species (ROS) is a feature of the early stages of AD, thus suggesting that the removal of excess ROS can be a viable method of improving AD. Natural polyphenols are able to scavenge ROS and thus promising for treating AD. However, some issues need to be addressed. Among them, important are that most polyphenols are hydrophobic, have low bioavailability in the body, are easily degraded, and that single polyphenols have insufficient antioxidant capacity. In this study, we employed two polyphenols, resveratrol (RES) and oligomeric proanthocyanidin (OPC), and creatively grafted them with hyaluronic acid (HA) to form nanoparticles to address the aforementioned issues. Meanwhile, we strategically grafted the nanoparticles with the B6 peptide, enabling the nanoparticles to cross the blood–brain barrier (BBB) and enter the brain for AD treatment. Our results illustrate that B6‐RES‐OPC‐HA nanoparticles can significantly scavenge ROS, reduce brain inflammation, and improve learning and memory ability in AD mice. B6‐RES‐OPC‐HA nanoparticles have the potential to prevent and alleviate early AD.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease

Zhang

Zhao

Guo

et al. 2022

Bioengineering & Transla Med

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“…Previously, Zhang et al designed a nanoparticles delivery system targeting different stages of osteoclasts, and confirmed that the system could effectively target the corresponding osteoclasts. 69 However, our delivery system may be inferior to other engineering sEVs system in terms of biocompatibility and the loading efficiencies of specific miRNA, as reported previously. 70 Therefore, the system exhibited the following advantages: (1) it is the first system to target osteoclast precursors to reduce VPA-associated side-effects on bone.…”

Section: Discussionmentioning

confidence: 64%

Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss

Xie,

Cheng,

et al. 2024

Sig Transduct Target Ther

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The clinical role and underlying mechanisms of valproic acid (VPA) on bone homeostasis remain controversial. Herein, we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density (BMD) in both patients and mice. This effect was attributed to VPA-induced elevation in osteoclast formation and activity. Through RNA-sequencing, we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro, and further, a marked upregulation of mature miR-6359 (miR-6359) in vivo was demonstrated using quantitative real-time PCR (qRT-PCR) and miR-6359 fluorescent in situ hybridization (miR-6359-FISH). Specifically, the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils, T lymphocytes, monocytes and bone marrow-derived mesenchymal stem cells (BMSCs) following VPA stimulation, which influenced osteoclast differentiation and bone-resorptive activity. Additionally, VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species (ROS) production by silencing the SIRT3 protein expression, followed by activation of the MAPK signaling pathway, which enhanced osteoclast formation and activity, thereby accelerating bone loss. Currently, there are no medications that can effectively treat VPA-induced bone loss. Therefore, we constructed engineered small extracellular vesicles (E-sEVs) targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif (CGGGAGC) in the 3’-end of the anti-miR-6359 sequence. We confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss, but not on ovariectomy (OVX) and glucocorticoid-induced osteoporotic models, deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.

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“…Both nanoparticles were modified with CD44-binding hyaluronic acid (HA), which further fostered delivery to the CD44-rich bone marrow. 343 The targeting ability of both nanoparticles on bone resorption areas was validated by bone tissue sectioning and small animal biopsy.…”

Section: Bone Matrixmentioning

confidence: 99%

Targeting strategies for bone diseases: signaling pathways and clinical studies

Wang

Liu

et al. 2023

Sig Transduct Target Ther

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Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has been considered a promising therapeutic approach for handling such drawbacks. With the deepening understanding of bone biology, improvements in some established bone-targeted drugs and novel therapeutic targets for drugs and deliveries have emerged on the horizon. In this review, we provide a panoramic summary of recent advances in therapeutic strategies based on bone targeting. We highlight targeting strategies based on bone structure and remodeling biology. For bone-targeted therapeutic agents, in addition to improvements of the classic denosumab, romosozumab, and PTH1R ligands, potential regulation of the remodeling process targeting other key membrane expressions, cellular crosstalk, and gene expression, of all bone cells has been exploited. For bone-targeted drug delivery, different delivery strategies targeting bone matrix, bone marrow, and specific bone cells are summarized with a comparison between different targeting ligands. Ultimately, this review will summarize recent advances in the clinical translation of bone-targeted therapies and provide a perspective on the challenges for the application of bone-targeted therapy in the clinic and future trends in this area.

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A novel nano delivery system targeting different stages of osteoclasts

Abstract: Osteoclast(OC) abnormalities represent osteoporosis's critical mechanism (OP). OCs undergo multiple processes that range from monocytic to functional. Different drugs target OCs at different developmental stages; however, almost no Suitable drug-targeted...

Cited by 9 publications

References 47 publications

Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease

Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease

Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss

Targeting strategies for bone diseases: signaling pathways and clinical studies

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