Nanolipogels as a cell-mimicking platform for controlled release of biomacromolecules

Cao, Yilin; Wong, Yuk Shan; Mabrouk, Amira Ben; Vincent, Anita P.; Liew, Melvin Wen Jie; Tan, Yisheng; Venkatraman, Subbu

doi:10.1039/d0na00093k

Cited by 4 publications

(9 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, lipid concentration in the nanoparticles was determined by modified Stewart Assay through quantifying the phospholipids complex form with ammonium ferrothiocyanate 34 .…”

Section: Methodsmentioning

confidence: 99%

Designing siRNA/chitosan-methacrylate complex nanolipogel for prolonged gene silencing effects

Cao

Tan

Wong

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

Despite immense revolutionary therapeutics potential, sustaining release of active small interfering RNA (siRNA) remains an arduous challenge. The development of nanoparticles with siRNA sustained release capabilities provides an avenue to enhance the therapeutic efficacy of gene-based therapy. Herein, we present a new system based on the encapsulation of siRNA/chitosan-methacrylate (CMA) complexes into liposomes to form UV crosslinkable Nanolipogels (NLGs) with sustained siRNA-release properties in vitro. We demonstrated that the CMA nanogel in NLGs can enhance the encapsulation efficiency of siRNA and provide sustained release of siRNA up to 28 days. To understand the particle mechanism of cellular entry, multiple endocytic inhibitors have been used to investigate its endocytosis pathways. The study saw positively charged NLGs entering cells via multiple endocytosis pathways, facilitating endosomal escape and slowly releasing siRNA into the cytoplasm. Transfection experiments confirmed that the crosslinked NLG delivery system provides effective transfection and prolonged silencing effect up to 14 days in cell cultures. We expect that this sustained-release siRNA NLG platform would be of interest in both fundamental biological studies and in clinical applications to extend the use of siRNA-based therapies.

show abstract

“…In this study, lipid concentration in the nanoparticles was determined by modified Stewart Assay through quantifying the phospholipids complex form with ammonium ferrothiocyanate 34 .…”

Section: Methodsmentioning

confidence: 99%

Designing siRNA/chitosan-methacrylate complex nanolipogel for prolonged gene silencing effects

Cao

Tan

Wong

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this study, lipid concentration in the nanoparticles was determined by modified Stewart Assay through quantifying the phospholipids complex form with ammonium ferrothiocyanate 34 Quantitative cell entry was performed via flow cytometry (Guava® easyCyte 8HT Benchtop Flow Cytometer, Merck-Millipore). In this study, 100,000 FibroGRO cells were treated with NLG containing 0.0625 mM lipids with 0.1 mol % (1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine-N-(carboxyfluorescein) (ammonium salt), Avanti) and then incubated 2 h at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Designing siRNA/Chitosan-Methacrylate Complex Nanolipogel for Prolonged Gene Silencing Effects

et al. 2021

View full text Add to dashboard Cite

“…One of those approaches taken was using nanolipogel (NLG), in which the hydrophilic small-molecule drugs or biomolecules are encapsulated within the gelated core of the NLG, surrounded by a lipid bilayer ( Ramanathan et al, 2016 ; Guo et al, 2018 ; Cao et al, 2020 ). Current studies have demonstrated that NLGs has successfully been used to encapsulate and suppress the burst release of hydrophilic drugs and biomolecules, such as doxorubicin hydrochloride ( Yu et al, 2018 ), Dextran-Fluorescein Isothiocyanate (DFITC) ( Anselmo et al, 2015 ), maraviroc and tenofovir disoproxil fumarate ( Ramanathan et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, we adopted the design of PEGDA NLG ( Cao et al, 2020 ) for a mechanistic study on the release of encapsulated biomolecule, where inspiration was drawn from the concept of macromolecular crowding phenomenon in cells ( Ellis, 2001 ; Zhou et al, 2008 ; Soleimaninejad et al, 2017 ). It is known that the intracellular diffusion of proteins, or other biomolecules, in the cytoplasm can be hindered by a phenomenon loosely termed as “macromolecular crowding”, where intracellular organelles and macromolecules exhibit a crowding effect to hinders the diffusion of intracellular proteins.…”

Section: Introductionmentioning

confidence: 99%

Cell-mimicking polyethylene glycol-diacrylate based nanolipogel for encapsulation and delivery of hydrophilic biomolecule

Liew

Wong

Parikh

et al. 2023

Front. Bioeng. Biotechnol.

Self Cite

View full text Add to dashboard Cite

Lipid based nanoparticulate formulations have been widely used for the encapsulation and sustain release of hydrophilic drugs, but they still face challenges such as high initial burst release. Nanolipogel (NLG) emerges as a potential system to encapsulate and deliver hydrophilic drug while suppressing its initial burst release. However, there is a lack of characterization of the drug release mechanism from NLGs. In this work, we present a study on the release mechanism of hydrophilic Dextran-Fluorescein Isothiocyanate (DFITC) from Poly (ethylene glycol) Diacrylate (PEGDA) NLGs by using different molecular weights of PEGDA to vary the mesh size of the nanogel core, drawing inspiration from the macromolecular crowding effect in cells, which can be viewed as a mesh network of undefined sizes. The effect is then further characterized and validated by studying the diffusion of DFITC within the nanogel core using Fluorescence Recovery after Photobleaching (FRAP), on our newly developed cell derived microlipogels (MLG). This is in contrast to conventional FRAP works on cells or bulk hydrogels, which is limited in our application. Our work showed that the mesh size of the NLGs can be controlled by using different Mw of PEGDA, such as using a smaller MW to achieve higher crosslinking density, which will lead to having smaller mesh size for the crosslinked nanogel, and the release of hydrophilic DFITC can be sustained while suppressing the initial burst release, up to 10-fold more for crosslinked PEGDA 575 NLGs. This is further validated by FRAP which showed that the diffusion of DFITC is hindered by the decreasing mesh sizes in the NLGs, as a result of lower mobile fractions. These findings will be useful for guiding the design of PEGDA NLGs to have different degree of suppression of the initial burst release as well as the cumulative release, for a wide array of applications. This can also be extended to other different types of nanogel cores and other nanogel core-based nanoparticles for encapsulation and release of hydrophilic biomolecules.

show abstract

Nanolipogels as a cell-mimicking platform for controlled release of biomacromolecules

Abstract: We present studies of protein (insulin) efflux rates from nano-sized core–shell systems with a gelled core and a lipid bilayer (nanolipogels).

Cited by 4 publications

References 33 publications

Designing siRNA/chitosan-methacrylate complex nanolipogel for prolonged gene silencing effects

Designing siRNA/chitosan-methacrylate complex nanolipogel for prolonged gene silencing effects

Designing siRNA/Chitosan-Methacrylate Complex Nanolipogel for Prolonged Gene Silencing Effects

Cell-mimicking polyethylene glycol-diacrylate based nanolipogel for encapsulation and delivery of hydrophilic biomolecule

Contact Info

Product

Resources

About