Supramolecular/macromolecular organic radical contrast agents (smORCAs) overcome many of the limitations of nitroxide radicals for use in magnetic resonance imaging in vivo like poor stability and weak contrast.
Virus-like particles are an emerging class of nano-biotechnology with the Tobacco Mosaic Virus (TMV) having found a wide range of applications in imaging, drug delivery, and vaccine development. TMV is typically produced in planta, and, as an RNA virus, is highly susceptible to natural mutation that may impact its properties. Over the course of 2 years, from 2018 until 2020, our laboratory followed a spontaneous point mutation in the TMV coat protein—first observed as a 30 Da difference in electrospray ionization mass spectrometry (ESI–MS). The mutation would have been difficult to notice by electrophoretic mobility in agarose or SDS-PAGE and does not alter viral morphology as assessed by transmission electron microscopy. The mutation responsible for the 30 Da difference between the wild-type (wTMV) and mutant (mTMV) coat proteins was identified by a bottom-up proteomic approach as a change from glycine to serine at position 155 based on collision-induced dissociation data. Since residue 155 is located on the outer surface of the TMV rod, it is feasible that the mutation alters TMV surface chemistry. However, enzyme-linked immunosorbent assays found no difference in binding between mTMV and wTMV. Functionalization of a nearby residue, tyrosine 139, with diazonium salt, also appears unaffected. Overall, this study highlights the necessity of standard workflows to quality-control viral stocks. We suggest that ESI–MS is a straightforward and low-cost way to identify emerging mutants in coat proteins.
Intracellular targeting is essential for the efficiently delivering of drugs and nanotherapeutics. Cytosolic transport of nanomaterials is often necessary for therapeutic delivery into cells but remains a challenge owing to...
Virus-like particles are an emerging class of nano-biotechnology with the Tobacco Mosaic Virus (TMV) having found a wide range of applications in imaging, drug delivery, and vaccine development. TMV is typically produced in planta, and, as an RNA virus, is highly susceptible to natural mutation that may impact its properties. Over the course of two years, from 2018 until 2020, our laboratory followed a spontaneous point mutation in the TMV coat protein—first observed as a 30 Da difference in electrospray ionization mass spectrometry (ESI-MS). The mutation would have been difficult to notice by electrophoretic mobility in agarose or SDS-PAGE and does not alter viral morphology as assessed by transmission electron microscopy. The mutation responsible for the 30 Da difference between the wild-type (wTMV) and mutant (mTMV) coat proteins was identified by a bottom-up proteomic approach as a change from glycine to serine at position 155 based on collision-induced dissociation data. Since residue 155 is located on the outer surface of the TMV rod, it is feasible that the mutation alters TMV surface chemistry. However, enzyme-linked immunosorbent assays found no difference in binding between mutant and wild-type TMV. Functionalization of a nearby residue, tyrosine 139, with diazonium salt, also appears unaffected. Overall, this study highlights the necessity of standard workflows to quality-control viral stocks. We suggest that ESI-MS is a straightforward and low-cost way to identify emerging mutants in coat proteins.
Nanoparticle-based therapeutics have been applied in a broad range of clinical and pre-clinical applications from diagnosis to treatment for cancer. A wide range of synthetic and naturally occurring materials such as polymers, metal oxides, silicate, liposomes, and carbon nanotubes have been developed to overcome key barriers in small molecule therapeutics including intracellular trafficking, cell/tissue targeting, poor biodistribution, and low efficiency. Virus like particles (VLPs)—engineered and non-infectious self-assembling systems based on viral nanostructures—are new approach toward overcoming these limitations, as they are a protein-based nanomaterial that closely mimics the highly symmetrical and polyvalent conformation of viruses while lacking the viral genomes. Their innate biocompatibility, biodegradability, monodispersity, mild immunogenicity, and safety combined with the capacity to chemically modify the interior and exterior surfaces of these systems offer scientists a highly customizable tool to design and engineer multi-component therapeutic agents. In this review, we discuss how these systems have been used in a wide array of cancer treatments including phototherapy, immunotherapy, gene therapy, and chemotherapy.
Vaccines have saved countless lives by preventing and even irradicating infectious dis-eases. Commonly used subunit vaccines comprising one or multiple recombinant proteins isolated from a pathogen demonstrate a better safety profile than live or attenuated vaccines. However, the immuno-genicity of these vaccines is weak, and therefore, subunit vaccines require a series of doses to achieve sufficient immunity against the pathogen. Here, we show that the biomimetic mineralization of the inert model antigen, ovalbumin (OVA), in zeolitic imidazolate framework-8 (ZIF-8) significantly improves the humoral immune response over three bolus doses of OVA (OVA 3×). Encapsulation of OVA in ZIF-8 (OVA@ZIF) demonstrated higher serum antibody titers against OVA than OVA 3×. OVA@ZIF vac-cinated mice displayed higher populations of germinal center (GC) B cells and IgG1+ GC B cells as op-posed to OVA 3×, indicative of class-switching recombination. We show that the mechanism of this phe-nomenon is at least partly owed to the sustained release of OVA from the ZIF-8 composite, acting as an antigen reservoir for antigen-presenting cells to traffic into the draining lymph node, enhancing the hu-moral response. Lastly, our model system OVA@ZIF is produced quickly at the gram scale in a labora-tory setting, sufficient for up to 20,000 vaccine doses.
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