Dataset Information

Loading of Silica Nanoparticles in Block Copolymer Vesicles during Polymerization-Induced Self-Assembly: Encapsulation Efficiency and Thermally Triggered Release.

ABSTRACT: Poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) diblock copolymer vesicles can be prepared in the form of concentrated aqueous dispersions via polymerization-induced self-assembly (PISA). In the present study, these syntheses are conducted in the presence of varying amounts of silica nanoparticles of approximately 18 nm diameter. This approach leads to encapsulation of up to hundreds of silica nanoparticles per vesicle. Silica has high electron contrast compared to the copolymer which facilitates TEM analysis, and its thermal stability enables quantification of the loading efficiency via thermogravimetric analysis. Encapsulation efficiencies can be calculated using disk centrifuge photosedimentometry, since the vesicle density increases at higher silica loadings while the mean vesicle diameter remains essentially unchanged. Small angle X-ray scattering (SAXS) is used to confirm silica encapsulation, since a structure factor is observed at q ≈ 0.25 nm(-1). A new two-population model provides satisfactory data fits to the SAXS patterns and allows the mean silica volume fraction within the vesicles to be determined. Finally, the thermoresponsive nature of the diblock copolymer vesicles enables thermally triggered release of the encapsulated silica nanoparticles simply by cooling to 0-10 °C, which induces a morphological transition. These silica-loaded vesicles constitute a useful model system for understanding the encapsulation of globular proteins, enzymes, or antibodies for potential biomedical applications. They may also serve as an active payload for self-healing hydrogels or repair of biological tissue. Finally, we also encapsulate a model globular protein, bovine serum albumin, and calculate its loading efficiency using fluorescence spectroscopy.

SUBMITTER: Mable CJ

PROVIDER: S-EPMC4697924 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Abstract Extracellular vesicles (EVs) have demonstrated unique advantages in serving as nanocarriers for drug delivery, yet the cargo encapsulation efficiency is far from expectation, especially for hydrophilic chemotherapeutic drugs. Besides, the intrinsic heterogeneity of EVs renders it difficult to evaluate drug encapsulation behaviour. Inspired by the active drug loading strategy of liposomal nanomedicines, here we report the development of a method, named “Sonication and Extrusion‐assisted Active Loading” (SEAL), for effective and stable drug encapsulation of EVs. Using doxorubicin‐loaded milk‐derived EVs (Dox‐mEVs) as the model system, sonication was applied to temporarily permeabilize the membrane, facilitating the influx of ammonium sulfate solution into the lumen to establish the transmembrane ion gradient essential for active loading. Along with extrusion to downsize large mEVs, homogenize particle size and reshape the nonspherical or multilamellar vesicles, SEAL showed around 10‐fold enhancement of drug encapsulation efficiency compared with passive loading. Single‐particle analysis by nano‐flow cytometry was further employed to reveal the heterogeneous encapsulation behaviour of Dox‐mEVs which would otherwise be overlooked by bulk‐based approaches. Correlation analysis between doxorubicin auto‐fluorescence and the fluorescence of a lipophilic dye DiD suggested that only the lipid‐enclosed particles were actively loadable. Meanwhile, immunofluorescence analysis revealed that more than 85% of the casein positive particles was doxorubicin free. These findings further inspired the development of the lipid‐probe‐ and immuno‐mediated magnetic isolation techniques to selectively remove the contaminants of non‐lipid enclosed particles and casein assemblies, respectively. Finally, the intracellular assessments confirmed the superior performance of SEAL‐prepared mEV formulations, and demonstrated the impact of encapsulation heterogeneity on therapeutic outcome. The as‐developed cargo‐loading approach and nano‐flow cytometry‐based characterization method will provide an instructive insight in the development of EV‐based delivery systems.

Project description:Despite the common association of ?-conjugated polymers with flexible and stretchable electronics, these materials can be rigid and brittle unless they are designed otherwise. For example, low modulus, high extensibility, and high toughness are treated as prerequisites for integration with soft and biological structures. One of the most successful and commercially available organic electronic materials is the conductive and brittle polyelectrolyte complex poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). To make this material stretchable, additives such as ionic liquids must be used. These additives may render the composite incompatible with biological tissue. In this work, we describe the synthesis of an intrinsically stretchable variant of the conductive polymer PEDOT:PSS that is free of additives. The approach involves the synthesis of a block copolymer comprising soft segments of poly(polyethylene glycol methyl ether acrylate) (PPEGMEA) and hard segments of poly(styrene sulfonate) (PSS) using a reversible addition-fragmentation chain transfer (RAFT) polymerization. Subsequently, we used the newly synthesized ionic elastomer PSS-b-PPEGMEA as a matrix for the oxidative polymerization of EDOT. The resulting polyelectrolyte elastomer, PEDOT:PSS-b-PPEGMEA, can withstand elongations up to 128% and has a toughness up to 10.1 MJ m-3. While the polyelectrolyte elastomer is not as conductive as the commercial material, the toughness and extensibility are each more than an order of magnitude higher. Moreover, the electrical conductivity of the polyelectrolyte elastomer exhibits minimal decrease with strain within the elastic regime. We then compared the block copolymer to physical blends of PEDOT:PSS and PPEGMEA. The blend material had a much lower failure strain of only 38% and a maximum toughness of 4.9 MJ m-3. This approach thus emphasizes the importance of the covalent linking of the PSS and PPEGMEA blocks. Furthermore, we demonstrate that the conductivity of scratched films can be restored upon exposure to water.

Dataset Information

Loading of Silica Nanoparticles in Block Copolymer Vesicles during Polymerization-Induced Self-Assembly: Encapsulation Efficiency and Thermally Triggered Release.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets