41 research outputs found
Single-chain polymer nanoparticles in controlled drug delivery and targeted imaging
As a relatively new class of materials, single-chain polymer nanoparticles (SCNPs) just entered the field of (biomedical) applications, with recent advances in polymer science enabling the formation of bio-inspired nanosized architectures. Exclusive intramolecular collapse of individual polymer chains results in individual nanoparticles. With sizes an order of magnitude smaller than conventional polymer nanoparticles, SCNPs are in the size regime of many proteins and viruses (1â20 nm). Multifaceted syntheses and design strategies give access to a wide set of highly modular SCNP materials. This review describes how SCNPs have been rendered water-soluble and highlights ongoing research efforts towards biocompatible SCNPs with tunable properties for controlled drug delivery, targeted imaging and protein mimicry.</p
Cytosolic Delivery of Single-Chain Polymer Nanoparticles
Cytosolic delivery of therapeutic agents is key to improving their efficacy, as the therapeutics are primarily active in specific organelles. Single-chain polymer nanoparticles (SCNPs) are a promising nanocarrier platform in biomedical applications due to their unique size range of 5-20 nm, modularity, and ease of functionalization. However, cytosolic delivery of SCNPs remains challenging. Here, we report the synthesis of active ester-functional SCNPs of approximately 10 nm via intramolecular thiol-Michael addition cross-linking and their functionalization with increasing amounts of tertiary amines 0 to 60 mol % to obtain SCNPs with increasing positive surface charges. No significant cytotoxicity was detected in bEND.3 cells for the SCNPs, except when SCNPs with high amounts of tertiary amines were incubated over prolonged periods of time at high concentrations. Cellular uptake of the SCNPs was analyzed, presenting different uptake behavior depending on the degree of functionalization. Confocal microscopy revealed successful cytosolic delivery of SCNPs with high degrees of functionalization (45%, 60%), while SCNPs with low amounts (0% to 30%) of tertiary amines showed high degrees of colocalization with lysosomes. This work presents a strategy to direct the intracellular location of SCNPs by controlled surface modification to improve intracellular targeting for biomedical applications
Enhancing Cellular Internalization of Single-Chain Polymer Nanoparticles via Polyplex Formation
Intracellular delivery
of nanoparticles is crucial in nanomedicine
to reach optimal delivery of therapeutics and imaging agents. Single-chain
polymer nanoparticles (SCNPs) are an interesting class of nanoparticles
due to their unique site range of 5â20 nm. The intracellular
delivery of SCNPs can be enhanced by using delivery agents. Here,
a positive polymer is used to form polyplexes with SCNPs, similar
to the strategy of protein and gene delivery. The size and surface
charge of the polyplexes were evaluated. The cellular uptake showed
rapid uptake of SCNPs via polyplex formation, and the cytosolic delivery
of the SCNPs was presented by confocal microscopy. The ability of
SCNPs to act as nanocarriers was further explored by conjugation of
doxorubicin
Role of surface charge distribution on band-structure and optical properties of silicon nanocrystals
Post-polymerization functionalized sulfonium nanogels for gene delivery
Gene therapy is widely recognized as a promising method in combating diseases caused by gene abnormalities or deletions. The effects of these deletions and mutations are ameliorated through gene therapy by means of transfection vectors. These delivery vehicles are tasked with protecting the gene and transporting it to the cell nucleus when necessary. Nano-sized hydrogel particles, also known as nanogels, are crosslinked polymeric nanoparticles that are promising materials for such biomedical applications. Whereas most cationic carriers for gene delivery are nitrogen-based, we are interested in utilizing a sulfonium moiety to this end. Diversifying the available gene vectors not only satisfies scientific curiosity, it could also offer improved gene delivery efficiencies. Here we describe the synthesis of glycidyl methacrylate (GMA) nanogels as a platform for subsequent functionalization. Ring-opening reactions with diethyl sulfide were carried out to install permanent cationic sulfonium groups on the nanogels, yielding readily water-soluble nanogels with a zeta potential of ζ = +40 ± 0.5 mV at neutral pH and a mean diameter of D = 29 ± 10 nm as determined by transmission electron microscopy (TEM). The degree of functionalization with sulfonium groups was found to be tunable. These nanogels were subjected to post-synthesis modifications resulting in biocompatible sulfonium nanogels containing a thioglycerol moiety. Polyplexes were formed by successful incubation with plasmid DNA encoding for green fluorescent protein (pCMV-GFP), at various ratios. In a next step, nucleic acid delivery by sulfonium nanogels was probed for various cell lines for the first time, showing poor delivery properties
Construction of viral protein-based hybrid nanomaterials mediated by a macromolecular glue
A generic strategy to construct virus protein-based hybrid nanomaterials is reported by using a macromolecular glue inspired by mussel adhesion. Commercially available poly(isobutylene-alt-maleic anhydride) (PiBMA) modified with dopamine (PiBMAD) is designed as this macromolecular glue, which serves as a universal adhesive material for the construction of multicomponent hybrid nanomaterials. As a proof of concept, gold nanorods (AuNRs) and single-walled carbon nanotubes (SWCNTs) are initially coated with PiBMAD. Subsequently, viral capsid proteins from the Cowpea Chlorotic Mottle Virus (CCMV) assemble around the nano-objects templated by the negative charges of the glue. With virtually unchanged properties of the rods and tubes, the hybrid materials might show improved biocompatibility and can be used in future studies toward cell uptake and delivery.</p
Development of an in vitro airway epithelialâendothelial cell culture model on a flexible porous poly(Trimethylene carbonate) membrane based on caluâ3 airway epithelial cells and lung microvascular endothelial cells
Due to the continuing high impact of lung diseases on society and the emergence of new respiratory viruses, such as SARSâCoVâ2, there is a great need for in vitro lung models that more accurately recapitulate the in vivo situation than current models based on lung epithelial cell cultures on stiff membranes. Therefore, we developed an in vitro airway epithelialâendothelial cell culture model based on Caluâ3 human lung epithelial cells and human lung microvascular endothelial cells (LMVECs), cultured on opposite sides of flexible porous poly(trimethylene carbonate) (PTMC) membranes. Caluâ3 cells, cultured for two weeks at an airâliquid interface (ALI), showed good expression of the tight junction (TJ) protein Zonula Occludens 1 (ZOâ1). LMVECs cultured submerged for three weeks were CD31âpositive, but the expression was diffuse and not localized at the cell membrane. Barrier functions of the Caluâ3 cell cultures and the coâcultures with LMVECs were good, as determined by electrical resistance measurements and fluorescein isothiocya-nateâdextran (FITCâdextran) permeability assays. Importantly, the Caluâ3/LMVEC coâcultures showed better cell viability and barrier function than monoâcultures. Moreover, there was no evidence for epithelialâ and endothelialâtoâmesenchymal transition (EMT and EndoMT, respec-tively) based on staining for the mesenchymal markers vimentin and αâSMA, respectively. These results indicate the potential of this new airway epithelialâendothelial model for lung research. In addition, since the PTMC membrane is flexible, the model can be expanded by introducing cyclic stretch for enabling mechanical stimulation of the cells. Furthermore, the model can form the basis for biomimetic airway epithelialâendothelial and alveolarâendothelial models with primary lung epithelial cells.</p
A high molecular weight reversible coordination polymer of PdCl2 and 1,12-bis(diphenylphosphino)dodecane
In the reversible system [PdCl2{Ph2P(CH2)12PPh2}], linear supramolecular polymers are shown to be in equilibrium with cyclic structures and high molecular weight material was obtained by melt polymerisatio