Ultrasound-mediated gene delivery

Yoon, Chang Shin; Park, Jeong H.

doi:10.1517/17425241003596329

Cited by 48 publications

(37 citation statements)

References 59 publications

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“…(50) Sonoporation with 75 µg BMP-2 plasmid led to radiographic bone formation in a mouse intramuscular model, although pDNA without sonoporation also led to some ectopic bone in this study. (51) Multiple cycles of injections and sonoporations were required to induce bone.…”

Section: Bmp9mentioning

confidence: 56%

Realizing the potential of gene-based molecular therapies in bone repair

Rose

Uludağ

2013

Journal of Bone and Mineral Research

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A better understanding of osteogenesis at genetic and biochemical levels is yielding new molecular entities that can modulate bone regeneration and potentially act as novel therapies in a clinical setting. These new entities are motivating alternative approaches for bone repair by utilizing DNA-derived expression systems, as well as RNA-based regulatory molecules controlling the fate of cells involved in osteogenesis. These sophisticated mediators of osteogenesis, however, pose unique delivery challenges that are not obvious in deployment of conventional therapeutic agents. Viral and nonviral delivery systems are actively pursued in preclinical animal models to realize the potential of the gene-based medicines. This article will summarize promising bone-inducing molecular agents on the horizon as well as provide a critical review of delivery systems employed for their administration. Special attention was paid to synthetic (nonviral) delivery systems because they are more likely to be adopted for clinical testing because of safety considerations. We present a comparative analysis of dose-response relationships, as well as pharmacokinetic and pharmacodynamic features of various approaches, with the purpose of clearly defining the current frontier in the field. We conclude with the authors' perspective on the future of genebased therapy of bone defects, articulating promising research avenues to advance the field of clinical bone repair. © 2013 American Society for Bone and Mineral Research. KEY WORDS: OSTEOGENESIS; BIOENGINEERING; MOLECULAR PATHWAYS; GENE-BASED THERAPYClinical Need for New Bone-Regeneration Strategies N early 2.2 million bone grafts are performed worldwide annually (1) and up to 20% of fractures are hampered by impaired healing. (2) The economic impact of nonunions is enormous, with the cost of spinal fusions alone reaching $20 billion annually. (3) The gold standard for repair of large segmental defects remains autologous grafts, where bone harvested from a non-weight-bearing site, usually the iliac crest, is used to repair defects. Bone grafts, however, are limited in several aspects, including potency of the grafts and the physiological detriment resulting from harvest surgery. Allografts are alternatively employed, where donor tissue is used to repair the defect, but the risk of disease transmission is always a concern. Allografts are extensively processed to reduce this risk, but osteopotency of the graft could be decreased in this way. (4) Demineralized bone matrix derived from decalcified bone can similarly act as a substitute; its potency, however, is variable and depends on the processing conditions. Synthetic scaffolds have been used to provide a hospitable environment for new bone formation. Scaffolds have been constructed from the organic (collagen) and inorganic (hydroxyapatite [HA]) components of bone, but such scaffolds are incapable of inducing osteogenesis on their own and they are more suitable for smaller defects.Osteogenic proteins are frequently employed to render ost...

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Section: Bmp9mentioning

confidence: 56%

Realizing the potential of gene-based molecular therapies in bone repair

Rose

Uludağ

2013

Journal of Bone and Mineral Research

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“…Additionally, SonoVue has recently been used to expand the yield of gene delivery. US-mediated gene delivery combined with MBs was evidenced to be significantly safer than other local gene-delivery methods [109]. The combination of US-mediated MB destruction and shRNA could enhance antitumor efficacy [110].…”

Section: Challenges and Perspectivesmentioning

confidence: 99%

Advanced Microbubbles as a Multifunctional Platform Combining Imaging and Therapy

Wang

et al. 2016

Applied Sciences

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Microbubbles as traditional ultrasound contrast agents have seen tremendous developments and bio-applications in the past decades. Due to their outstanding performance, advanced microbubbles as a multifunctional platform combining both imaging and therapy have been increasingly attracting attention. Associated with ultrasound-mediated stimuli, targeting drug transportation with high precision can be established and, as a consequence, a synergistic treatment strategy may prevail, which implies a bright perspective for this brand-new technology. This perspective article will summarize the latest developments on the advanced microbubbles, and review their emerging biomedical applications for the vast community of both applied ultrasound and functional ultrasound-based materials.

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“…The pressure gradient and shear stress enhance the permeability of the cell membrane, enabling transport of plasmid DNA or therapeutics into the cell. 30 As shown in Figure 1A, microbubbles are one type of widely used ultrasound contrast agent, and are microsized (1-10 µm) gas bubbles with a shell composed of phospholipids, polymers, or proteins (Table 1). First-generation microbubbles are air-filled microspheres, with mean diameters in the range of 1-8 µm, that are capable of passing through pulmonary capillaries.…”

Section: Multiple Ultrasound-responsive Drug Delivery Systems Microbumentioning

confidence: 99%

“…[17][18][19] A combination of two or more formulations can be used as URDDS, such as liposomal bubbles 20,21 and microemulsions. 22 The drugs loaded can include inorganic substances, eg, titanium dioxide, 23 small molecules (curcumin, 24 doxorubicin, 25 cisplatin, 5 epirubicin hydrochloride, 26 10-hydroxycamptothecin 27 ), proteins, 28,29 small interfering RNA, 8,21 DNA, 30 and antisense oligodeoxynucleotides. 31,32 Their therapeutic applications include anticancer therapy, 23,33 treatment of ischemic myocardium, 29 induction of an immune response, 34 cartilage tissue engineering, 35 transdermal drug delivery, 36,37 treatment of Huntington's disease 38 and thrombolysis, 39,40 and disruption of the blood-brain barrier.…”

Section: Introductionmentioning

confidence: 99%

Potential and problems in ultrasound-responsive drug delivery systems

Zhao¹,

Du²,

Lu³

et al. 2013

IJN

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Abstract:Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington's disease, thrombolysis, and disruption of the blood-brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future.

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Ultrasound-mediated gene delivery

Abstract: Ultrasound-mediated gene delivery combined with microbubble agents provides significant safety advantages over other methods of local gene delivery.

Cited by 48 publications

References 59 publications

Realizing the potential of gene-based molecular therapies in bone repair

Realizing the potential of gene-based molecular therapies in bone repair

Advanced Microbubbles as a Multifunctional Platform Combining Imaging and Therapy

Potential and problems in ultrasound-responsive drug delivery systems

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