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Elsa, United States

Nguyen H.T.,University of Washington | Shen H.,Elsa Biologics LLC
Journal of Materials Chemistry B | Year: 2016

Au nanoshell/silica core (GNS) nanoparticles have been used for the photothermal ablation of tumors and imaging, and have recently reached clinical trials. In this study, we compared the ability of bare (GNS) and PEGylated Au nanoshell/silica core (PEG-GNS) nanoparticles to stimulate the production of IL-1β in the macrophage cell line. GNS particles formed large aggregates while PEG-GNS particles did not form in cell culture medium. Correspondingly, GNS particles induced the production of IL-1β while PEG-GNS did not induce in THP-1 macrophage cell lines. Corroborating with the in vitro results, GNS induced a significant level of neutrophil influx in the peritoneal cavity, and PEG-GNS reduced the level four times. The density of PEG on the particle surface has little effect on both the induction of IL-1β and neutrophil influx by PEG-GNS. The ability of GNS and PEG-GNS particles to induce and scavenge reactive oxygen species (ROS) was also assessed. We demonstrated that GNS was able to induce and scavenge ROS while PEG-GNS was not. The excess of ROS induced by GNS potentially caused the activation of inflammasomes, and thus the secretion of IL-1β. Our finding on the reduction of IL-1β production by the PEGylation of nanoparticles has implications in other particulates used for drug delivery, imaging and therapy. © 2016 The Royal Society of Chemistry.

Sun B.,University of Washington | Shen H.,Elsa Biologics LLC
Journal of Nanomaterials | Year: 2015

Surface-induced biomineralization represents a flexible approach to immobilizing DNA onto biomaterial surfaces for surface-mediated DNA delivery. Immobilized naked DNA is uniformly embedded in thin films of nanocomposites, which limits the internalization of DNA to some cell types, such as neuronal cells. In this study, DNA molecules were initially complexed with liposomes to form lipoplexes. Subsequently, these lipoplexes were immobilized onto a cell culture compatible surface through surface-induced biomineralization. Under all the conditions we examined, lipoplexes were efficiently immobilized onto the surface and formed lipoplex-nanocomposites. We have shown that the size of liposomes and the composition of mineralizing solutions have significant effects on the morphology and topology of nanocomposites and thus the organization and the intracellular levels of DNA. The transgene expression mediated by lipoplex-nanocomposites was greatly enhanced in neuronal cells compared to the immobilized naked DNA. © 2015 Bingbing Sun and Hong Shen.

Zhan X.,University of Washington | Shen H.,Elsa Biologics LLC
Vaccine | Year: 2015

In order for a more precise control over the quality and quantity of immune responses stimulated by synthetic particle-based vaccines, it is critical to control the colloidal stability of particles and the release of protein antigens in both extracellular space and intracellular compartments. Different proteins exhibit different sizes, charges and solubilities. This study focused on modulating the release and colloidal stability of proteins with varied isoelectric points. A polymer particle delivery platform made from the blend of three polymers, poly(lactic-co-glycolic acid) (PLGA) and two random pH-sensitive copolymers, were developed. Our study demonstrated its programmability with respective to individual proteins. We showed the colloidal stability of particles at neutral environment and the release of each individual protein at different pH environments were dependent on the ratio of two charge polymers. Subsequently, two antigenic proteins, ovalbumin (OVA) and Type 2 Herpes Simplex Virus (HSV-2) glycoprotein D (gD) protein, were incorporated into particles with systematically varied compositions. We demonstrated that the level of in vitro CD8+ T cell and in vivo immune responses were dependent on the ratio of two charged polymers, which correlated well with the release of proteins. This study provided a promising design framework of pH-responsive synthetic vaccines for protein antigens of interest. © 2015 Elsevier Ltd.

Sun B.,University of Washington | Shen H.,Elsa Biologics LLC
Biomaterials | Year: 2015

Biominerals (or microcalcification) deposited in soft tissues are associated with a number of pathogeneses and cancer progressions. Biominerals have also shown promise for DNA delivery and tissue engineering. Biominerals themselves may stimulate NALP3 inflammasomes, and DNA delivered by biominerals can potentially engage with intracellular DNA sensors, resulting in unwanted inflammatory responses. In this study, a library of biominerals doped with or without DNA is formed through surface-induced biomineralization. It is demonstrated that empty biominerals stimulate NALP3 inflammasomes and induce the production of IL-1β. They are also able to activate mouse embryonic fibroblasts (MEFs) and induce inflammatory cytokines, i.e. IL-6. DNA delivered by biominerals escapes the detection of TLR9, but activates DAI and inflammasomes. Furthermore, it is shown that the level of both IL-1β and IL-6 is correlated with the composition of biominerals, in particular the ratio of Mg(Sr) to Ca, and the pH sensitivity of biominerals. These results provide insights into the design of safe and effective DNA delivery systems and biocompatible implants as well as the understanding of the pathogeneses of biominerals deposited in soft tissues. © 2015 Elsevier Ltd.

Zhan X.,University of Washington | Tran K.K.,University of Washington | Tran K.K.,Biogen Idec | Wang L.,University of Washington | Shen H.,Elsa Biologics LLC
Pharmaceutical Research | Year: 2015

Purpose: A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes by a particle delivery platform made from the controlled blending of poly(lactic-co-glycolic acid) (PLGA) and a random pH-sensitive copolymer. Methods: We utilized both microscopic and biochemical methods to semi-quantitatively assess how the composition of blend particles affects the level of endosomal escape of cargos of various sizes and enzymes into the cytosolic space. Results: We demonstrated that these polymeric particles enabled the controlled delivery of cargos into the cytosolic space that was more dependent on the cargo size and less on the composition of blend particles. Blend particles did not induce the rupture of endosomal/lysosomal compartments and released less than 20% of endosomal/lysosomal enzymes. Conclusions: This study provides insight into understanding the efficacy and safety of a delivery system for intracellular delivery of biologics and drugs. Blend particles offer a potential platform to target intracellular compartments while potentially minimizing cellular toxicity. © 2015 Springer Science+Business Media New York.

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