Lipid-nucleic acid nanoparticles of novel ionizable lipids for systemic BMP-9 gene delivery to bone-marrow mesenchymal stem cells for osteoinduction

Vhora, Imran; Lalani, Rohan; Bhatt, Priyanka; Patil, Sushilkumar; Misra, Ambikanandan

doi:10.1016/j.ijpharm.2019.04.006

Cited by 49 publications

(33 citation statements)

References 46 publications

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“…The efficacy of their nucleic acid delivery along with their simple synthesis, small size and serum stability have made LNPs particularly important in personalized genetic therapy applications 12,23 . Ionizable LNPs are an ideal platform for the delivery of these nucleic acid therapies as they have a near-neutral charge at physiological pH but become charged in acidic endosomal compartments, promoting endosomal escape for intracellular delivery 24,25 . However, despite these advantages, LNP systems can still be limited by low drug loading and biodistribution that results in high uptake to the liver and spleen 16 .…”

Section: Np Classes Lipid-based Npsmentioning

confidence: 99%

“…Delivery of genome-editing systems is challenging because these systems are multicomponent, hold sensitive cargo and need to overcome several extracellular and intracellular biological barriers to reach the genome of target cells. Lipid-based and polymer-based NPs have delivered a range of nucleic acids in vivo, and are in various stages of clinical development 24,44,104,183 . For example, a LNP siRNA drug termed Onpattro (patisiran) was recently approved by the FDA for the treatment of amyloidosis 270 .…”

Section: Nps For Genome Editingmentioning

confidence: 99%

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Engineering precision nanoparticles for drug delivery

Mitchell

Billingsley

Haley

et al. 2020

Nat Rev Drug Discov

4,050

2,814

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In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers — systemic, microenvironmental and cellular — that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.

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Section: Np Classes Lipid-based Npsmentioning

confidence: 99%

Section: Nps For Genome Editingmentioning

confidence: 99%

Engineering precision nanoparticles for drug delivery

Mitchell

Billingsley

Haley

et al. 2020

Nat Rev Drug Discov

4,050

2,814

View full text Add to dashboard Cite

show abstract

“…Meanwhile, BMP9 suppresses receptor activator of nuclear factor-κB (NF-κB) ligand-(RANKL-) induced osteoclast differentiation of bone marrow macrophages (BMMs) by inhibiting the Akt-NF-κB-NFATc1 pathway [32]. Therefore, BMP9 may be explored as an effective therapeutic strategy for osteoporosis [35][36][37][38].…”

Section: Bmps and Bonementioning

confidence: 99%

Potential Functions of the BMP Family in Bone, Obesity, and Glucose Metabolism

Chen

Wang³

et al. 2021

Journal of Diabetes Research

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Characteristic bone metabolism was observed in obesity and diabetes with controversial conclusions. Type 2 diabetes (T2DM) and obesity may manifest increased bone mineral density. Also, obesity is more easily to occur in T2DM. Therefore, we infer that some factors may be linked to bone and obesity as well as glucose metabolism, which regulate all of them. Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor- (TGF-) beta superfamily, regulate a diverse array of cellular functions during development and in the adult. More and more studies revealed that there exists a relationship between bone metabolism and obesity as well as glucose metabolism. BMP2, BMP4, BMP6, BMP7, and BMP9 have been shown to affect the pathophysiological process of obesity and glucose metabolism beyond bone metabolism. They may exert functions in adipogenesis and differentiation as well as insulin resistance. In the review, we summarize the literature on these BMPs and their association with metabolic diseases including obesity and diabetes.

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“…Furthermore, higher osteoinductive activity of BMP-6 and BMP-9, compared to BMP-2 or BMP-7, make them promising candidates for promoting bone repair or filling, as shown by several recent studies [ 399 , 400 , 401 ]. For example, a recent randomized, double-blinded, placebo-controlled phase I/II clinical trial revealed that autologous blood coagulum combined with rhBMP-6 (1.0 mg/10 mL) promoted bone healing in patients with high tibial osteotomy [ 401 ].…”

Section: The Use Of Members Of the Tgf-β Superfamily In Clinical Amentioning

confidence: 99%

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions

Jann

Gascon

Roux

et al. 2020

IJMS

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The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors—in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins—not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of osteoclastogenesis, osteogenic differentiation of stem cells, and osteoblasts/osteoclasts balance. After introducing the main types of bone cells, their differentiation and cooperation during bone remodeling and fracture healing processes are discussed. Then, the TGF-β superfamily, its signaling via canonical and non-canonical pathways, as well as its regulation by Wnt/Notch or microRNAs are described and discussed. Its important role in bone homeostasis, repair, or disease is also highlighted. Finally, the clinical therapeutic uses of members of the TGF-β superfamily and their associated complications are debated.

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Lipid-nucleic acid nanoparticles of novel ionizable lipids for systemic BMP-9 gene delivery to bone-marrow mesenchymal stem cells for osteoinduction

Cited by 49 publications

References 46 publications

Engineering precision nanoparticles for drug delivery

Engineering precision nanoparticles for drug delivery

Potential Functions of the BMP Family in Bone, Obesity, and Glucose Metabolism

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions

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