Development of surface modified biodegradable polymeric nanoparticles to deliver GSE24.2 peptide to cells: A promising approach for the treatment of defective telomerase disorders

Egusquiaguirre, Susana P.; Manguán-García, Cristina; Pintado‐Berninches, Laura; Iarriccio, Laura; Carbajo, Daniel; Alberício, Fernando; Royo, Míriam; Pedraz, José Luís; Hernández, Rosa María; Perona, Rosario; Igartua, Manoli

doi:10.1016/j.ejpb.2015.01.028

Cited by 27 publications

(22 citation statements)

References 44 publications

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“…Since the toxicity profile of PEI–PLGA particles has been previously reported by our group , our next goal was to study the potency of the DiR‐loaded PEI–PLGA as an optoacoustic contrastagents in vitro . First of all, the absorbance spectra of DiR‐loaded PEI–PLGA nanoparticles were obtained from spectrophotometer measurements, and then their optoacoustic properties were investigated in the MSOT imaging system.…”

Section: Resultsmentioning

confidence: 99%

“…Taking all this into account, in this study we have chosen to investigate the fate of the PLGA particles in a rodent model using optoacoustic imaging, enabled by grafting an NIR fluorescent dye (DiR, 1,1′-dioctadecyltetramethyl indotricarbocyanine iodide). As the surface charge of the particles plays an important role in their interactions with cells, we opted for an additional cationic polymer polyethyleneimine (PEI) functionalization of their surface to increase their potential cellular uptake, as was previously reported by our group (15). By using three different administration routes (intraperitoneal, intravenous and subcutaneous), we show that the stability of the dye loading of the nanoparticles allows for efficient tracking in real time and in vivo of the behavior of the probe in healthy animal in MSOT, and validate the model for further theranostic studies.…”

Section: Introductionmentioning

confidence: 99%

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Optoacoustic imaging enabled biodistribution study of cationic polymeric biodegradable nanoparticles

Egusquiaguirre

Bézière

Pedraz

et al. 2015

Contrast Media & Molecular

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Nanosized contrast agents for molecular imaging have attracted widespread interest for diagnostic applications with high resolution in medicine. However, many solid nanoparticles exhibit a great potential to induce toxicity, hindering their use for clinical applications. On the other hand, near-infrared (NIR) dyes have also been used for extensive biological applications, but show some limitations due to their poor aqueous stability, tendency to aggregation and rapid elimination from the body. An alternative proposed in this work to overcome these limitations is the use of NIR dye-loaded nanoparticles. Here we introduce nanoparticles constructed with poly(D,L-lactide-co-glycolic acid) (PLGA), a biodegradable and biocompatible polymer widely used for biomedical applications, attached to the polycation polyethyleneimine (PEI) to obtain positively charged nanoparticles. The in vivo biodistribution of the cationic PEI-PLGA nanoparticles was investigated after administration through three different routes (intravenous, intraperitoneal and subcutaneous) using multispectral optoacoustic tomography (MSOT). The prepared nanoparticles exhibited good colloidal stability and adequate optical properties for optoacoustic imaging. The in vivo biodistribution assays indicated a strong accumulation of the particles in the liver and spleen, and retention in these organs for at least 24 h. Therefore, these nanoparticles could find promising applications in MSOT due to a sharp and characteristic optoacoustic spectrum and high optoacoustic signal generation, and become a promising building block for theranostic strategies.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Optoacoustic imaging enabled biodistribution study of cationic polymeric biodegradable nanoparticles

Egusquiaguirre

Bézière

Pedraz

et al. 2015

Contrast Media & Molecular

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“…Initial phase release could be linked to rapid hydration of nanoparticles due to the hydrophilic nature of chitosan. This phenomenon might also be due to the release of ALD which is adsorbed on nanoparticles surface [29]. In fact, "drug release" refers to the process in which drug molecules migrate from the initial position in the polymeric system to the polymer's outer surface and then to the release medium.…”

Section: In Vitro Releasementioning

confidence: 99%

Enhancement of alendronate encapsulation in chitosan nanoparticles

Miladi

Sfar

Fessi

et al. 2015

Journal of Drug Delivery Science and Technology

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“…In addition, DNA damage, oxidative stress and cell senescence were reduced upon expression of GSE4 [201]. GSE24.2 could be delivered to cells using surface modified biodegradable polymeric nanoparticles, which might facilitate their administration to patients [202]. These results open a new therapeutic opportunity for the treatment of telomere biology disorders and GSE24.2 was recently approved by the EMA as an orphan drug for DC treatment (EU/ 3/12/1070-EMA/OD/136/11].…”

Section: Experimental Strategies For Treatment Of Telomere Biology DImentioning

confidence: 99%

Molecular Diagnosis and Precision Therapeutic Approaches for Telomere Biology Disorders

Perona¹,

Iarriccio²,

Pintado‐Berninches³

et al. 2016

Telomere - A Complex End of a Chromosome

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Telomeres are nucleo-protein structures located at the end of chromosomes that protect them from degradation. Telomeres length is maintained by the activity of the telomerase complex. These structures are protected by a specialized protein complex named shelterin. In the absence of telomerase activity and/or protection telomeres are shortened after each round of DNA replication. When a critical size is reached, telomeres are recognized as damaged DNA by the cell p53-dependent DNA-repair system. Persistent activation of this pathway finally results in cell apoptosis or senescence. There are a number of rare hereditary diseases caused by the presence of shortened telomeres, collectively named telomeropathies or telomere biology disorders. In these diseases, cell proliferation is impaired, which results in premature aging and dysfunction of highly proliferative tissues (bone morrow, skin and other epithelia). Among them are Dyskeratosis congenita, the Hoyeraal-Hreidarsson, Revesz and Coats plus syndromes, Aplastic anemia, Idiopathic pulmonary fibrosis and nonalcoholic, noninfectious liver disease. Mutations present in the genes coding for component of the telomerase and shelterin complexes and other proteins involved in telomere replication are the cause of these diseases. Clinical manifestations, causative mutations, diagnosis and possible therapeutic approaches to these diseases will be discussed in this chapter.

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Development of surface modified biodegradable polymeric nanoparticles to deliver GSE24.2 peptide to cells: A promising approach for the treatment of defective telomerase disorders

Cited by 27 publications

References 44 publications

Optoacoustic imaging enabled biodistribution study of cationic polymeric biodegradable nanoparticles

Optoacoustic imaging enabled biodistribution study of cationic polymeric biodegradable nanoparticles

Enhancement of alendronate encapsulation in chitosan nanoparticles

Molecular Diagnosis and Precision Therapeutic Approaches for Telomere Biology Disorders

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