Surface charge tunability as a powerful strategy to control electrostatic interaction for high efficiency silencing, using tailored oligopeptide-modified poly(beta-amino ester)s (PBAEs)

Dosta, Pere; Segovia, Nathaly; Cascante, Anna; Ramos, Víctor; Borrós, Salvador

doi:10.1016/j.actbio.2015.03.029

Cited by 63 publications

(130 citation statements)

References 41 publications

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“…Nowadays, there are a wide range of vectors, but none of them possess all these conditions. Therefore, the authors focused on enhancing our previously described poly(β-amino ester)s, 18,19 whose cellspecificity can be modulated by changing their oligopeptide formulation and making them efficient and useful in physiological media.…”

Section: Resultsmentioning

confidence: 99%

“…Nevertheless, the C32 polymer was formulated at a 200 : 1 polymer : siRNA ratio, since this formulation required a higher polymer : siRNA ratio to produce sufficiently stable particles for size analysis. 18 Polyplexes obtained using C32-CR3 as a polymer (5-amino-1-pentanol amine) showed a particle average size of 220 nm with a positive zeta potential, +18.5 mV. In general, dynamic light scattering analyses showed that some of the newly developed polymers were able to achieve smaller nanoparticles than the C32 polymer, while maintaining their positive surface charge.…”

Section: Biophysical Characterization Of Oligopeptide End-modified Pbaesmentioning

confidence: 96%

“…3. Results showed that the basic poly(beta-amino ester), C32 polymer, described by Lynn et al and further end-modified with arginine oligopeptides, 18,19 exhibited low stability, reaching a size greater than 1000 nm, revealing a high degree of nanoparticle aggregation, i.e. average hydrodynamic diameter greater than 1000 nm, after a 2 hour incubation in PBS.…”

Section: Stability Effect Of Different Hydrophobic Modificationsmentioning

confidence: 99%

“…S2 †), which have been shown to confer cell-specificity in different cells lines. 18,19 In general, the hydrodynamic diameters of different oligopeptide-modified C6-50 and Ccho-50 nanoparticles were in the nanometric range, and were significantly smaller than those of polyplexes obtained from C32 polymers. These results suggest that hydrophobized polymers present a high capacity to condense RNAi-based drugs, making them promising delivery vectors for RNAi therapy, where the loading capacity is key for clinical translation to avoid systemic overexposure of vector materials.…”

Section: Egfp Silencing In Mda Mb231 Cells Using the Most Stable Polymentioning

confidence: 99%

“…[18][19][20] However, pBAEs possess limited in vivo stability, which hampers their further development in clinical applications. Recently, it has been described that shielding the surface of pBAE-RNAi polyplexes using a hydrogel matrix is a promising way to stabilize the resulting formulation.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Stable and efficient generation of poly(β-amino ester)s for RNAi delivery

Dosta

Ramos

Borrós

2018

Mol. Syst. Des. Eng.

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abCationic polymers are promising delivery systems for RNAi due to their ease of manipulation, scale-up conditions and transfection efficiency. However, some properties, such as stability and targeting, remain challenging to overcome. In this report, different modifications in poly(β-amino ester) (pBAE) structures have been explored to overcome these limitations. Recent studies have demonstrated that hydrophobicity plays a key role in controlling electrostatic interactions of plasma proteins with nanoparticles. Results show that a slight increase in the polymer hydrophobicity increases its siRNA packaging capacity, stability, and transfection efficiency. Consequently, polyplexes prepared with these hydrophobic structures are functional after incubation times longer than 48 hours in serum-containing medium. In addition, newly designed polymers were end-modified using different oligopeptide moieties in order to confer cell-specificity, as previously reported. Therefore, it can be concluded that these newly optimized pBAE polymers present great potential as delivery vectors to specifically drive therapeutic RNA-based nucleic acids in a cell-specific manner under physiological conditions.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Biophysical Characterization Of Oligopeptide End-modified Pbaesmentioning

confidence: 96%

Section: Stability Effect Of Different Hydrophobic Modificationsmentioning

confidence: 99%

Section: Egfp Silencing In Mda Mb231 Cells Using the Most Stable Polymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Stable and efficient generation of poly(β-amino ester)s for RNAi delivery

Dosta

Ramos

Borrós

2018

Mol. Syst. Des. Eng.

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Progress of Oligonucleotide Therapeutics Target to Rna

Zhou¹,

Yang²

2022

Nucleic Acids in Medicinal Chemistry and Chemical Biology

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mRNA Delivery System for Targeting Antigen‐Presenting Cells In Vivo

Fornaguera

Guerra-Rebollo

Lázaro

et al. 2018

Adv Healthcare Materials

Self Cite

105

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The encapsulation of mRNA in nanosystems as gene vaccines for immunotherapy purposes has experienced an exponential increase in recent years. Despite the many advantages envisaged within these approaches, their application in clinical treatments is still limited due to safety issues. These issues can be attributed, in part, to liver accumulation of most of the designed nanosystems and to the inability to transfect immune cells after an intravenous administration. In this context, this study takes advantage of the known versatile properties of the oligopeptide end-modified poly (β-amino esters) (OM-PBAEs) to complex mRNA and form discrete nanoparticles. Importantly, it is demonstrated that the selection of the appropriate end-oligopeptide modifications enables the specific targeting and major transfection of antigen-presenting cells (APC) in vivo, after intravenous administration, thus enabling their use for immunotherapy strategies. Therefore, with this study, it can be confirmed that OM-PBAE are appropriate systems for the design of mRNA-based immunotherapy approaches aimed to in vivo transfect APCs and trigger immune responses to fight either tumors or infectious diseases.

show abstract

Surface charge tunability as a powerful strategy to control electrostatic interaction for high efficiency silencing, using tailored oligopeptide-modified poly(beta-amino ester)s (PBAEs)

Cited by 63 publications

References 41 publications

Stable and efficient generation of poly(β-amino ester)s for RNAi delivery

Stable and efficient generation of poly(β-amino ester)s for RNAi delivery

Progress of Oligonucleotide Therapeutics Target to Rna

mRNA Delivery System for Targeting Antigen‐Presenting Cells In Vivo

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