We report a high-throughput platform for delivering large cargo elements into 100,000 cells in 1 min. Our biophotonic laser-assisted surgery tool (BLAST) generates an array of microcavitation bubbles that explode in response to laser pulsing, forming pores in adjacent cell membranes through which cargo is gently driven by pressurized flow. The platform delivers large items including bacteria, enzymes, antibodies and nanoparticles into diverse cell types with high efficiency and cell viability. We used this platform to explore the intracellular lifestyle of Francisella novicida and discovered that the iglC gene is unexpectedly required for intracellular replication even after phagosome escape into the cell cytosol.
Mesoporous silica are widely utilised as drug carriers due to their large pore volume and surface area, which facilitate effective loading. Additionally, they can be used to enhance drugs stability and protect against enzymatic degradation due to their silica framework. However, without the addition of a capping material, the loaded cargo may be prematurely released before reaching the target site.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University, Baltimore, MD; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Chemical & Biomolecular Engineering and Materials Science & Engineering, Johns Hopkins University, Baltimore, MD; Departments of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD. Electronic address:
Current treatments for retinal and choroidal neovascular diseases suffer from insufficient durability, including anti-vascular endothelial growth factor-A (VEGF-A) agents. It is, therefore, of interest to explore alternative methods that could allow for robust improvement in visual acuity with fewer injections required. Amongst various pre-clinical and clinical studies in the literature, a promising approach is the use of suprachoroidal injection with viral and non-viral gene delivery vectors.
Aging is a major risk factor for cardiovascular disease, the leading cause of death worldwide, and numerous other diseases, but the mechanisms of these aging-related effects remain elusive. Chronic changes in the microenvironment and paracrine signaling behaviors have been implicated, but remain understudied. Here, for the first time, we directly compare extracellular vesicles obtained from young and aged patients to identify therapeutic or disease-associated agents, and directly compare vesicles isolated from heart tissue matrix (TEVs) or plasma (PEVs).
Actin is essential for the survival and pathogenicity of the Apicomplexan parasite Toxoplasma gondii, where it plays essential functions in cargo transport, invasion, egress, and organelle inheritance. Recent work has shown that, unlike vertebrate skeletal muscle actin, purified T. gondii actin filaments (TgAct1) can undergo rapid treadmilling, due to large differences in the barbed- and pointed-end critical concentrations, rapid subunit dissociation from filament ends, and a rapid nucleotide exchange rate constant from free monomers.
Adaptor protein complex-3 (AP-3) mediates cargo sorting from endosomes to lysosomes and lysosome-related organelles. Recently, it was shown that AP-3 adopts a constitutively open conformation compared to the related AP-1 and AP-2 coat complexes, which are inactive until undergoing large conformational changes upon membrane recruitment. How AP-3 is regulated is therefore an open question.
