Spheroplexes: Hybrid PLGA-cationic lipid nanoparticles, for in vitro and oral delivery of siRNA

Arruda, Danielle Campiol; Lachagès, Anne-Marie; Demory, Hélène; Escriou, Guillaume; Laï-Kuen, René; Dugas, Pierre‐Yves; Hoffmann, Céline; Bessoles, Stéphanie; Sarrabayrouse, Guillaume; Malachias, A.; Finet, Stéphanie; Gastelois, Pedro Lana; Macedo, W. A. A.; Silva-Cunha, Armando; Bigey, Pascal; Escriou, Virginie

doi:10.1016/j.jconrel.2022.08.030

Cited by 16 publications

(4 citation statements)

References 73 publications

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“…We thus fixed the ratio R ± = 1.5 and analyzed the resulting LPX by flow cytometry, a method which enables codetection of different fluorophores within individual particles of nanometric size. 30 The resulting dot-plots for NGs-633 only, FITC-labeled liposomes only, and FITC-LPX-633 are given in the Figure 1 B. For NGs and liposomes, the dot plots demonstrate a higher fluorescence signal for AlexaFluor633 (71.96%) and FITC (75.99%) signals, respectively.…”

Section: Resultsmentioning

confidence: 98%

“…It was found that aggregation of the LPX occurred at R ± higher than 1.5. We thus fixed the ratio R ± = 1.5 and analyzed the resulting LPX by flow cytometry, a method which enables codetection of different fluorophores within individual particles of nanometric size . The resulting dot-plots for NGs-633 only, FITC-labeled liposomes only, and FITC-LPX-633 are given in the Figure B.…”

Section: Resultsmentioning

confidence: 99%

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Intracellular Delivery of Functional Proteins with DNA–Protein Nanogels–Lipids Complex

Mariconti,

Dechamboux,

Heckmann

et al. 2024

J. Am. Chem. Soc.

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Using functional proteins for therapeutic purposes due to their high selectivity and/or catalytic properties can enable the control of various cellular processes; however, the transport of active proteins inside living cells remains a major challenge. In contrast, intracellular delivery of nucleic acids has become a routine method for a number of applications in gene therapy, genome editing, or immunization. Here we report a functionalizable platform constituting of DNA−protein nanogel carriers crosslinked through streptavidin−biotin or streptactin−biotin interactions and demonstrate its applicability for intracellular delivery of active proteins. We show that the nanogels can be loaded with proteins bearing either biotin, streptavidin, or strep-tag, and the resulting functionalized nanogels can be delivered into living cells after complexation with cationic lipid vectors. We use this approach for delivery of alkaline phosphatase enzyme, which is shown to keep its catalytic activity after internalization by mouse melanoma B16 cells, as demonstrated by the DDAO−phosphate assay. The resulting functionalized nanogels have dimensions on the order of 100 nm, contain around 100 enzyme molecules, and are shown to be transfectable at low lipid concentrations (charge ratio R± = 0.75). This ensures the low toxicity of our system, which in combination with high local enzyme concentration (∼100 μM) underlines potential interest of this nanoplatform for biomedical applications.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Intracellular Delivery of Functional Proteins with DNA–Protein Nanogels–Lipids Complex

Mariconti,

Dechamboux,

Heckmann

et al. 2024

J. Am. Chem. Soc.

Self Cite

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show abstract

“…However, the therapeutic application of most of the synthesized polymers consisting of high-molecular weight and branching designing leads to efficient gene delivery efficiency with large cytotoxicity issues [ 131 ]. Hence, researchers are working on designing biodegradable polymers using natural biopolymers or using surface modification techniques to reduce the cytotoxicity of synthesized polymers [ 11 , 116 , 122 ]. Moffett et al have successfully demonstrated the delivery of mRNA into T cells by using a biodegradable poly (β-amino ester) (PBAE) polymer in mice model [ 144 ].…”

Section: Delivery Systems For Mrna Vaccines and Drugsmentioning

confidence: 99%

mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications

Wang,

Kumari,

Chen

et al. 2023

J Biomed Sci

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AbstractmRNA-based drugs have tremendous potential as clinical treatments, however, a major challenge in realizing this drug class will promise to develop methods for safely delivering the bioactive agents with high efficiency and without activating the immune system. With regard to mRNA vaccines, researchers have modified the mRNA structure to enhance its stability and promote systemic tolerance of antigenic presentation in non-inflammatory contexts. Still, delivery of naked modified mRNAs is inefficient and results in low levels of antigen protein production. As such, lipid nanoparticles have been utilized to improve delivery and protect the mRNA cargo from extracellular degradation. This advance was a major milestone in the development of mRNA vaccines and dispelled skepticism about the potential of this technology to yield clinically approved medicines. Following the resounding success of mRNA vaccines for COVID-19, many other mRNA-based drugs have been proposed for the treatment of a variety of diseases. This review begins with a discussion of mRNA modifications and delivery vehicles, as well as the factors that influence administration routes. Then, we summarize the potential applications of mRNA-based drugs and discuss further key points pertaining to preclinical and clinical development of mRNA drugs targeting a wide range of diseases. Finally, we discuss the latest market trends and future applications of mRNA-based drugs.

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“…The molar ratio of the components, the molecular weight and macromolecular architecture of the block copolymer, the main transition temperature of the phospholipid, and the surface charge, accompanied by the selection of an appropriate preparation protocol, are the crucial parameters for the formation of hybrid lipid/polymer vesicles and other nanomorphologies [ 1 , 5 , 6 , 7 , 8 , 9 ]. Furthermore, spheroplexes are fabricated with hybrid PLGA-cationic lipid nanoparticles for in vitro and oral delivery of siRNA [ 10 ]. Hybrid nanoparticles composed of the biocompatible polymer poly(methyl methacrylate) (PMMA) and the cationic lipid dioctadecyl dimethyl ammonium bromide (DODAB) and produced via the emulsion polymerization of methyl methacrylate (MMA) monomer in the presence of DODAB were used as immunoadjuvants.…”

Section: Introductionmentioning

confidence: 99%

Structure-Based Evaluation of Hybrid Lipid–Polymer Nanoparticles: The Role of the Polymeric Guest

Chountoulesi,

Pippa,

Forys

et al. 2024

Polymers

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The combination of phospholipids and block-copolymers yields advanced hybrid nanoparticles through the self-assembly process in an aqueous environment. The physicochemical features of the lipid/polymer components, like the lipid–polymer molar ratio, the macromolecular architecture of the block copolymer, the main transition temperature of the phospholipid, as well as the formulation and preparation protocol parameters, are some of the most crucial parameters for the formation of hybrid lipid/polymer vesicles and for the differentiation of their morphology. The morphology, along with other physicochemical nanoparticle characteristics are strictly correlated with the nanoparticle’s later biological behavior after being administered, affecting interactions with cells, biodistribution, uptake, toxicity, drug release, etc. In the present study, a structural evaluation of hybrid lipid–polymer nanoparticles based on cryo-TEM studies was undertaken. Different kinds of hybrid lipid–polymer nanoparticles were designed and developed using phospholipids and block copolymers with different preparation protocols. The structures obtained ranged from spherical vesicles to rod-shaped structures, worm-like micelles, and irregular morphologies. The obtained morphologies were correlated with the formulation and preparation parameters and especially the type of lipid, the polymeric guest, and their ratio.

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Spheroplexes: Hybrid PLGA-cationic lipid nanoparticles, for in vitro and oral delivery of siRNA

Cited by 16 publications

References 73 publications

Intracellular Delivery of Functional Proteins with DNA–Protein Nanogels–Lipids Complex

Intracellular Delivery of Functional Proteins with DNA–Protein Nanogels–Lipids Complex

mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications

Structure-Based Evaluation of Hybrid Lipid–Polymer Nanoparticles: The Role of the Polymeric Guest

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