Glioblastoma (GBM), the most aggressive form of brain cancer, has witnessed very little clinical progress over the last decades, in part, due to the absence of effective drug delivery strategies. ...Intravenous injection is the least invasive drug delivery route to the brain, but has been severely limited by the blood-brain barrier (BBB). Inspired by the capacity of natural proteins and viral particulates to cross the BBB, we engineered a synthetic protein nanoparticle (SPNP) based on polymerized human serum albumin (HSA) equipped with the cell-penetrating peptide iRGD. SPNPs containing siRNA against Signal Transducer and Activation of Transcription 3 factor (STAT3i) result in in vitro and in vivo downregulation of STAT3, a central hub associated with GBM progression. When combined with the standard of care, ionized radiation, STAT3i SPNPs result in tumor regression and long-term survival in 87.5% of GBM-bearing mice and prime the immune system to develop anti-GBM immunological memory.
The cellular environment impacts a myriad of cellular functions by providing signals that can modulate cell phenotype and function. Physical cues such as topography, roughness, gradients, and ...elasticity are of particular importance. Thus, synthetic substrates can be potentially useful tools for exploring the influence of the aforementioned physical properties on cellular function. Many micro‐ and nanofabrication processes have been employed to control substrate characteristics in both 2D and 3D environments. This review highlights strategies for modulating the physical properties of surfaces, the influence of these changes on cell responses, and the promise and limitations of these surfaces in in‐vitro settings. While both hard and soft materials are discussed, emphasis is placed on soft substrates. Moreover, methods for creating synthetic substrates for cell studies, substrate properties, and impact of substrate properties on cell behavior are the main focus of this review.
The cellular environment plays a significant role in cell phenotype and function. As such, physical properties of cell culture substrates including topography, roughness, and elasticity may be utilized to investigate the influence of these physical cues on the cellular response. In this review, strategies for modulating the physical properties of surfaces, the influence of these changes on cell responses, and the promise and limitations of these surfaces in in‐vitro settings are highlighted, with a particular emphasis on elastic substrates.
Abstract
Electrospinning has received a lot of attention in recent years because it can create nonwoven nanofiber webs with high surface area and porosity. However, the typical needle and ...syringe‐based electrospinning systems feature poor productivity that has limited their usefulness in the industrial field. Here, current developments in the creation of nanofibers employing nonconventional electrospinning methods, such as needleless electrospinning and syringeless electrospinning, are examined. These alternate electrospinning techniques, which are dependent on numerous polymer droplets of varied shapes, have the potential to match the productivity required for industry‐scale manufacturing of nanofibers. Additionally, they make it possible to produce nanofibers that are difficult to spin using traditional techniques, like electrospinning of colloidal suspensions.
Biomaterials form the basis of current and future biomedical technologies. They are routinely used to design therapeutic carriers, such as nanoparticles, for applications in drug delivery. Current ...strategies for synthesizing drug delivery carriers are based either on discovery of materials or development of fabrication methods. While synthetic carriers have brought upon numerous advances in drug delivery, they fail to match the sophistication exhibited by innate biological entities. In particular, red blood cells (RBCs), the most ubiquitous cell type in the human blood, constitute highly specialized entities with unique shape, size, mechanical flexibility, and material composition, all of which are optimized for extraordinary biological performance. Inspired by this natural example, we synthesized particles that mimic the key structural and functional features of RBCs. Similar to their natural counterparts, RBC-mimicking particles described here possess the ability to carry oxygen and flow through capillaries smaller than their own diameter. Further, they can also encapsulate drugs and imaging agents. These particles provide a paradigm for the design of drug delivery and imaging carriers, because they combine the functionality of natural RBCs with the broad applicability and versatility of synthetic drug delivery particles.
Nanoparticles with structural or chemical anisotropy are promising materials in domains as diverse as cellular delivery, photonic materials, or interfacial engineering. The surface chemistry may play ...a major role in some of these contexts. Introducing reactivity into such polymeric nanomaterials is thus of great potential, yet is still a concept in its infancy. In the current contribution, a simple nanoprecipitation technique leads to nanoparticles with diameters as low as 150 nm and well‐defined reactive surface patches of less than 30 nm in width, as well as surface‐reactive flat, disc‐like nanoparticles with corresponding dimensions, via an additional crosslinking/delamination sequence. To this aim, chemically doped block copolymers (BCPs) are employed. Control over morphology is attained by tuning preparation conditions, such as polymer concentration, solvent mixture composition, and blending with non‐functional BCP. Surface reactivity is demonstrated using a modular ligation method for the site‐selective immobilization of thiol molecules. The current approach constitutes a straightforward methodology requiring minimal engineering to produce nanoparticles with confined surface reactivity and/or shape anisotropy.
Nanoparticles with surface‐expressed reactive patches and corresponding nanodiscs are prepared by a simple nanoprecipitation technique with functional block copolymers. The surface pattern formation is controlled by preparation conditions (concentration, solvent, and functionality). Spatially confined functionalization is demonstrated by grafting model thiol compounds. These nanomaterials are structurally approaching biological particles and are interesting building blocks for colloidal assemblies.
Drug delivery by nanocarriers (NCs) has long been stymied by dominant liver uptake and limited target organ deposition, even when NCs are targeted using affinity moieties. Here we report a universal ...solution: red blood cell (RBC)-hitchhiking (RH), in which NCs adsorbed onto the RBCs transfer from RBCs to the first organ downstream of the intravascular injection. RH improves delivery for a wide range of NCs and even viral vectors. For example, RH injected intravenously increases liposome uptake in the first downstream organ, lungs, by ~40-fold compared with free NCs. Intra-carotid artery injection of RH NCs delivers >10% of the injected NC dose to the brain, ~10× higher than that achieved with affinity moieties. Further, RH works in mice, pigs, and ex vivo human lungs without causing RBC or end-organ toxicities. Thus, RH is a clinically translatable platform technology poised to augment drug delivery in acute lung disease, stroke, and several other diseases.
We demonstrate herein the fabrication of novel multicompartmental biodegradable microstructures via electrohydrodynamic cospinning of two or more polymer solutions. Under optimized processing ...conditions, the interface between the solutions can be sustained continuously for long time intervals, yielding fibers with multiple chemically distinct compartments. Simultaneous control over internal fiber architecture and the spatial arrangement of individual compartments combined with precise long-range fiber alignment makes these fibers potential candidates for applications such as tissue engineering or cell culture studies.
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