Poly(Lactic-co-Glycolic Acid) Nanoparticle Delivery of Peptide Nucleic Acids In Vivo

Oyaghire, Stanley; Quijano, Elias; Piotrowski-Daspit, Alexandra S.; Saltzman, W. Mark; Glazer, Peter M.

doi:10.1007/978-1-0716-0243-0_17

Cited by 13 publications

(11 citation statements)

References 63 publications

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“…In prior studies, we determined that acid terminated PLGA and ester terminated PLGA NPs (containing equal ratios of poly-lactic acid and poly-glycolic acid, 50:50) can effectively deliver PS and PNA-based anti-miRs [ 11 , 25 ]. In this study, we sought to develop NP formulations that can encapsulate and deliver the optimum amount of PS-141 and PNA-141 and their scrambled controls.…”

Section: Resultsmentioning

confidence: 99%

Nanoparticle Delivered Anti-miR-141-3p for Stroke Therapy

Dhuri

Vyas

Blumenfeld

et al. 2021

Cells

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Ischemic stroke and factors modifying ischemic stroke responses, such as social isolation, contribute to long-term disability worldwide. Several studies demonstrated that the aberrant levels of microRNAs contribute to ischemic stroke injury. In prior studies, we established that miR-141-3p increases after ischemic stroke and post-stroke isolation. Herein, we explored two different anti-miR oligonucleotides; peptide nucleic acid (PNAs) and phosphorothioates (PS) for ischemic stroke therapy. We used US FDA approved biocompatible poly (lactic-co-glycolic acid) (PLGA)-based nanoparticle formulations for delivery. The PNA and PS anti-miRs were encapsulated in PLGA nanoparticles by double emulsion solvent evaporation technique. All the formulated nanoparticles showed uniform morphology, size, distribution, and surface charge density. Nanoparticles also exhibited a controlled nucleic acid release profile for 48 h. Further, we performed in vivo studies in the mouse model of ischemic stroke. Ischemic stroke was induced by transient (60 min) occlusion of middle cerebral artery occlusion followed by a reperfusion for 48 or 72 h. We assessed the blood-brain barrier permeability of PLGA NPs containing fluorophore (TAMRA) anti-miR probe after systemic delivery. Confocal imaging shows uptake of fluorophore tagged anti-miR in the brain parenchyma. Next, we evaluated the therapeutic efficacy after systemic delivery of nanoparticles containing PNA and PS anti-miR-141-3p in mice after stroke. Post-treatment differentially reduced both miR-141-3p levels in brain tissue and infarct injury. We noted PNA-based anti-miR showed superior efficacy compared to PS-based anti-miR. Herein, we successfully established that nanoparticles encapsulating PNA or PS-based anti-miRs-141-3p probes could be used as a potential treatment for ischemic stroke.

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Section: Resultsmentioning

confidence: 99%

Nanoparticle Delivered Anti-miR-141-3p for Stroke Therapy

Dhuri

Vyas

Blumenfeld

et al. 2021

Cells

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“…Recently, PLGA based NPs have been used for encapsulating PNAs to achieve higher intracellular delivery for antisense [26] and gene editing applications [27] . The list of reagents and equipment required for formulation of PNA loaded PLGA NPs is provided below ( Table 3 ).…”

Section: Encapsulation Of Pnas In Plga Npsmentioning

confidence: 99%

Formulation of PLGA nanoparticles containing short cationic peptide nucleic acids

2020

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Peptide nucleic acids (PNAs) have emerged as one of the most versatile tools with a wide range of biomedical applications including antisense, antimiR, antigene, as well as site-specific gene editing. The application and potential of PNAs has been limited due to low solubility and poor cellular uptake. Several strategies have been employed to overcome the aforementioned challenges like conjugation to cationic peptides or nanotechnology to achieve superior transfection efficiency ex vivo and in vivo. Here, we report a detailed procedure optimized in our lab for synthesis of short cationic PNA probes, which exhibit high purity and yield in comparison to full-length PNA oligomers. We also provide step-by-step details of encapsulating short cationic PNA probes in poly (lactic-co-glycolic acid) nanoparticles by double emulsion solvent evaporation technique. Detailed procedure for synthesis of short cationic PNAs with or without fluorophore (dye) conjugation while ensuring high yield and purity. Step-by-step details for encapsulation of short cationic PNAs in PLGA nanoparticles via double emulsion solvent evaporation technique.

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“…PLGA-NPs were previously used for systemic delivery of FDAapproved drugs and effectively delivered PNA/donor DNA combinations into primary human and mouse hematopoietic cells with essentially no toxicity [301,312,313]. For in vivo studies, PNAs and donor DNAs, at a molar ratio of 2:1, were incorporated into PLGA-NPs and administrated by intravenous injection while SCF was administrated intraperitoneally 3 h before PLGA-NP injections.…”

Section: Thalassemiamentioning

confidence: 99%

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

Brodyagin

Katkevičs

Kotikam

et al. 2021

Beilstein J. Org. Chem.

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Peptide nucleic acid (PNA) is arguably one of the most successful DNA mimics, despite a most dramatic departure from the native structure of DNA. The present review summarizes 30 years of research on PNA’s chemistry, optimization of structure and function, applications as probes and diagnostics, and attempts to develop new PNA therapeutics. The discussion starts with a brief review of PNA’s binding modes and structural features, followed by the most impactful chemical modifications, PNA enabled assays and diagnostics, and discussion of the current state of development of PNA therapeutics. While many modifications have improved on PNA’s binding affinity and specificity, solubility and other biophysical properties, the original PNA is still most frequently used in diagnostic and other in vitro applications. Development of therapeutics and other in vivo applications of PNA has notably lagged behind and is still limited by insufficient bioavailability and difficulties with tissue specific delivery. Relatively high doses are required to overcome poor cellular uptake and endosomal entrapment, which increases the risk of toxicity. These limitations remain unsolved problems waiting for innovative chemistry and biology to unlock the full potential of PNA in biomedical applications.

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Poly(Lactic-co-Glycolic Acid) Nanoparticle Delivery of Peptide Nucleic Acids In Vivo

Cited by 13 publications

References 63 publications

Nanoparticle Delivered Anti-miR-141-3p for Stroke Therapy

Nanoparticle Delivered Anti-miR-141-3p for Stroke Therapy

Formulation of PLGA nanoparticles containing short cationic peptide nucleic acids

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

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