The Experts below are selected from a list of 60417 Experts worldwide ranked by ideXlab platform
Nicole F Steinmetz - One of the best experts on this subject based on the ideXlab platform.
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designing s100a9 targeted Plant Virus nanoparticles to target deep vein thrombosis
Biomacromolecules, 2021Co-Authors: Jooneon Park, Amy M Wen, Huiyun Gao, Matthew D Shin, Daniel I Simon, Yunmei Wang, Nicole F SteinmetzAbstract:Thromboembolic conditions are a leading cause of death worldwide, and deep vein thrombosis (DVT), or occlusive venous clot formation, is a critical and rising problem that contributes to damage of vital organs, long-term complications, and life-threatening conditions such as pulmonary embolism. Early diagnosis and treatment are correlated to better prognosis. However, current technologies in these areas, such as ultrasonography for diagnostics and anticoagulants for treatment, are limited in terms of their accuracy and therapeutic windows. In this work, we investigated targeting myeloid related protein 14 (MRP-14, also known as S100A9) using Plant Virus-based nanoparticle carriers as a means to achieve tissue specificity aiding prognosis and therapeutic intervention. We used a combinatorial peptide library screen to identify peptide ligands that bind MRP-14. Candidates were selected and formulated as nanoparticles by using cowpea mosaic Virus (CPMV) and tobacco mosaic Virus (TMV). Intravascular delivery of our MRP-14-targeted nanoparticles in a murine model of DVT resulted in enhanced accumulation in the thrombi and reduced thrombus size, suggesting application of nanoparticles for molecular targeting of MRP-14 could be a promising direction for improving DVT diagnostics, therapeutics, and therefore prognosis.
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combination of Plant Virus nanoparticle based in situ vaccination with chemotherapy potentiates antitumor response
Nano Letters, 2017Co-Authors: Karin L Lee, Sourabh Shukla, Abner A Murray, Mee Rie Sheen, Ulrich Commandeur, Steven Fiering, Nicole F SteinmetzAbstract:Immunotherapeutics are gaining more traction in the armamentarium used to combat cancer. Specifically, in situ vaccination strategies have gained interest because of their ability to alter the tumor microenvironment to an antitumor state. Herein, we investigate whether flexuous Plant Virus-based nanoparticles formed by the potato Virus X (PVX) can be used as an immunotherapeutic for in situ vaccine monotherapy. We further developed dual chemo-immunotherapeutics by incorporating doxorubicin (DOX) into PVX yielding a dual-functional nanoparticle (PVX–DOX) or by coadministration of the two therapeutic regimes, PVX immunotherapy and DOX chemotherapy (PVX+DOX). In the context of B16F10 melanoma, PVX was able to elicit delayed tumor progression when administered as an intratumoral in situ vaccine. Furthermore, the coadministration of DOX via PVX+DOX enhanced the response of the PVX monotherapy through increased survival, which was also represented in the enhanced antitumor cytokine/chemokine profile stimulated ...
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Elongated Plant Virus-Based Nanoparticles for Enhanced Delivery of Thrombolytic Therapies
2017Co-Authors: Andrzej S. Pitek, Huiyun Gao, Daniel I Simon, Yunmei Wang, Sahil Gulati, Phoebe L. Stewart, Nicole F SteinmetzAbstract:Thrombotic cardiovascular disease, including acute myocardial infarction, ischemic stroke, and venous thromboembolic disease, is the leading cause of morbidity and mortality worldwide. While reperfusion therapy with thrombolytic agents reduces mortality from acute myocardial infarction and disability from stroke, thrombolysis is generally less effective than mechanical reperfusion and is associated with fatal intracerebral hemorrhage in up to 2–5% of patients. To address these limitations, we propose the tobacco mosaic Virus (TMV)-based platform technology for targeted delivery of thrombolytic therapies. TMV is a Plant Virus-based nanoparticle with a high aspect ratio shape measuring 300 × 18 nm. These soft matter nanorods have favorable flow and margination properties allowing the targeting of the diseased vessel wall. We have previously shown that TMV homes to thrombi in a photochemical mouse model of arterial thrombosis. Here we report the synthesis of TMV conjugates loaded with streptokinase (STK). Various TMV-STK formulations were produced through bioconjugation of STK to TMV via intervening PEG linkers. TMV-STK was characterized using SDS–PAGE and Western blot, transmission electron microscopy, cryo-electron microscopy, and cryo-electron tomography. We investigated the thrombolytic activity of TMV-STK in vitro using static phantom clots, and in a physiologically relevant hydrodynamic model of shear-induced thrombosis. Our findings demonstrate that conjugation of STK to the TMV surface does not compromise the activity of STK. Moreover, the nanoparticle conjugate significantly enhances thrombolysis under flow conditions, which can likely be attributed to TMV’s shape-mediated flow properties resulting in enhanced thrombus accumulation and dissolution. Together, these data suggest TMV to be a promising platform for the delivery of thrombolytics to enhance clot localization and potentially minimize bleeding risk
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serum albumin camouflage of Plant Virus based nanoparticles prevents their antibody recognition and enhances pharmacokinetics
Biomaterials, 2016Co-Authors: Andrzej S Pitek, Slater A Jameson, Frank A Veliz, Sourabh Shukla, Nicole F SteinmetzAbstract:Abstract Plant Virus-based nanoparticles (VNPs) are a novel class of nanocarriers with unique potential for biomedical applications. VNPs have many advantageous properties such as ease of manufacture and high degree of quality control. Their biocompatibility and biodegradability make them an attractive alternative to synthetic nanoparticles (NPs). Nevertheless, as with synthetic NPs, to be successful in drug delivery or imaging, the carriers need to overcome several biological barriers including innate immune recognition. Plasma opsonization can tag (V)NPs for clearance by the mononuclear phagocyte system (MPS), resulting in shortened circulation half lives and non-specific sequestration in non-targeted organs. PEG coatings have been traditionally used to ‘shield’ nanocarriers from immune surveillance. However, due to broad use of PEG in cosmetics and other industries, the prevalence of anti-PEG antibodies has been reported, which may limit the utility of PEGylation in nanomedicine. Alternative strategies are needed to tailor the in vivo properties of (Plant Virus-based) nanocarriers. We demonstrate the use of serum albumin (SA) as a viable alternative. SA conjugation to tobacco mosaic Virus (TMV)-based nanocarriers results in a ‘camouflage’ effect more effective than PEG coatings. SA-‘camouflaged’ TMV particles exhibit decreased antibody recognition, as well as enhanced pharmacokinetics in a Balb/C mouse model. Therefore, SA-coatings may provide an alternative and improved coating technique to yield (Plant Virus-based) NPs with improved in vivo properties enhancing drug delivery and molecular imaging.
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the protein corona of Plant Virus nanoparticles influences their dispersion properties cellular interactions and in vivo fates
Small, 2016Co-Authors: Andrzej S Pitek, Sourabh Shukla, Amy M Wen, Nicole F SteinmetzAbstract:Biomolecules in bodily fluids such as plasma can adsorb to the surface of nanoparticles and influence their biological properties. This phenomenon, known as the protein corona, is well established in the field of synthetic nanotechnology but has not been described in the context of Plant Virus nanoparticles (VNPs). The interaction between VNPs derived from Tobacco mosaic Virus (TMV) and plasma proteins is investigated, and it is found that the VNP protein corona is significantly less abundant compared to the corona of synthetic particles. The formed corona is dominated by complement proteins and immunoglobulins, the binding of which can be reduced by PEGylating the VNP surface. The impact of the VNP protein corona on molecular recognition and cell targeting in the context of cancer and thrombosis is investigated. A library of functionalized TMV rods with polyethylene glycol (PEG) and peptide ligands targeting integrins or fibrin(ogen) show different dispersion properties, cellular interactions, and in vivo fates depending on the properties of the protein corona, influencing target specificity, and non-specific scavenging by macrophages. Our results provide insight into the in vivo properties of VNPs and suggest that the protein corona effect should be considered during the development of efficacious, targeted VNP formulations.
Marilyn J. Roossinck - One of the best experts on this subject based on the ideXlab platform.
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Plant Virus Metagenomics: Advances in Virus Discovery.
Phytopathology, 2015Co-Authors: Marilyn J. Roossinck, Darren P. Martin, Philippe RoumagnacAbstract:In recent years Plant Viruses have been detected from many environments, including domestic and wild Plants and interfaces between these systems—aquatic sources, feces of various animals, and insects. A variety of methods have been employed to study Plant Virus biodiversity, including enrichment for Virus-like particles or Virus-specific RNA or DNA, or the extraction of total nucleic acids, followed by next-generation deep sequencing and bioinformatic analyses. All of the methods have some shortcomings, but taken together these studies reveal our surprising lack of knowledge about Plant Viruses and point to the need for more comprehensive studies. In addition, many new Viruses have been discovered, with most Virus infections in wild Plants appearing asymptomatic, suggesting that Virus disease may be a byproduct of domestication. For Plant pathologists these studies are providing useful tools to detect Viruses, and perhaps to predict future problems that could threaten cultivated Plants.
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Plant Virus ecology.
PLoS pathogens, 2013Co-Authors: Marilyn J. RoossinckAbstract:Viruses have generally been studied either as disease-causing infectious agents that have a negative impact on the host (most eukaryote-infecting Viruses), or as tools for molecular biology (especially bacteria-infecting Viruses, or phage). Virus ecology looks at the more complex issues of Virus-host-environment interactions. For Plant Viruses this includes studies of Plant Virus biodiversity, including Viruses sampled directly from Plants and from a variety of other environments; how Plant Viruses impact species invasion; interactions between Plants, Viruses and insects; the large number of persistent Viruses in Plants that may have epigenetic effects; and Viruses that provide a clear benefit to their Plant hosts (mutualists). Plants in a non-agricultural setting interact with many other living entities such as animals, insects, and other Plants, as well as their physical environment. Wild Plants are almost always colonized by a number of microbes, including fungi, bacteria and Viruses. Viruses may impact any of these interactions [1].
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Plant Virus Metagenomics: Biodiversity and Ecology
Annual review of genetics, 2012Co-Authors: Marilyn J. RoossinckAbstract:Viral metagenomics is the study of Viruses in environmental samples, using next generation sequencing that produces very large data sets. For Plant Viruses, these studies are still relatively new, but are already indicating that our current knowledge grossly underestimates the diversity of these Viruses. Some Plant Virus studies are using thousands of individual Plants so that each sequence can be traced back to its precise host. These studies should allow for deeper ecological and evolutionary analyses. The finding of so many new Plant Viruses that do not cause any obvious symptoms in wild Plant hosts certainly changes our perception of Viruses and how they interact with their hosts. The major difficulty in these (as in all) metagenomic studies continues to be the need for better bioinformatics tools to decipher the large data sets. The implications of this new information on Plant Viruses for international agriculture remain to be addressed.
Thierry Candresse - One of the best experts on this subject based on the ideXlab platform.
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Current impact and future directions of high throughput sequencing in Plant Virus diagnostics
Virus research, 2014Co-Authors: Sébastien Massart, Antonio Olmos, Haissam Jijakli, Thierry CandresseAbstract:Abstract The ability to provide a fast, inexpensive and reliable diagnostic for any given viral infection is a key parameter in efforts to fight and control these ubiquitous pathogens. The recent developments of high-throughput sequencing (also called Next Generation Sequencing – NGS) technologies and bioinformatics have drastically changed the research on viral pathogens. It is now raising a growing interest for Virus diagnostics. This review provides a snapshot vision on the current use and impact of high throughput sequencing approaches in Plant Virus characterization. More specifically, this review highlights the potential of these new technologies and their interplay with current protocols in the future of molecular diagnostic of Plant Viruses. The current limitations that will need to be addressed for a wider adoption of high-throughput sequencing in Plant Virus diagnostics are thoroughly discussed.
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Characterisation of Plant Virus populations by a metagenomic approach : Survey in French sub-antarctic islands
2009Co-Authors: Armelle Marais, Chantal Faure, Carole Couture, Laurence Svanella, Maurice Hullé, Marc Le Romancer, Thierry CandresseAbstract:Only a few number of metagenomic studies concern Plant Viruses. However, a global knowledge of viral diversity would be very interesting in terms of ecology and could have important impacts on viral taxonomy and diversity studies and, potentially, on the prediction of emerging Plant diseases. As an example, the “Plant Virus Biodiversity and Ecology” (PVDE) project has been initiated to survey the biodiversity of vascular Plant Viruses in the nature Conservancy’s Tallgrass Prairie Preserve of Oklahoma in USA (Wren et al., 2006). Our purpose is to describe the viral metagenome of the French sub-antarctic islands, especially in the Kerguelen islands. This project is included in the nationally funded EVINCE project “Vulnerability of native communities to invasive insects and climate change in sub-Antarctic islands” The ecosystems of these islands provide a suite of environments and scenarios that give key opportunities to improve our understanding of the consequences of climate change and biological invasions on terrestrial ecosystems. An additional interest is that almost nothing is known on the Plant Viruses present in such remote ecosystems, with the exception of a single report describing a new member of the BadnaVirus genus (Skotnicki et al., 2003). Viral screening was done by two approaches. The first one, opened, consists in the analysis of double-stranded RNA, random cloning, sequencing, and comparison with sequences in databanks. By this approach we have been able to detect in an introduced Tropaeolum majus sample, sequences presenting 34% of identity in amino acids (56% of similarity) with the replicase of Oryza sativa endornaVirus. The same approach permitted the identification of a new Plant or fungal Virus in a native Plant of Kerguelen islands (Aceana magellanica). The sequences revealed 50% of identity with the capsid of Black raspberry Virus F. The second approach consists in the screening of Viruses belonging to known viral genera by polyvalent detection RT-PCR tests. One Tropaeolum majus sample was identified as being infected by a Virus belonging to the NepoVirus genus. Indeed, the sequencing of the amplified fragment showed a significant identity in amino acids (89% and 93% of similarity) with the RNA-dependent RNA polymerase region of Cherry leaf roll Virus (CLRV), a well known member of NepoVirus genus. Tropaeolum majus was known to be an experimental host of CLRV, but for our knowledge it is the first time that CLRV is described to infect naturally Tropaeolum majus. In this case, it seems that the Virus was introduced in same time than the host Plant, demonstrating, if necessary, the impact of species introduction on such terrestrial ecosystems.
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The new Plant Virus family Flexiviridae and assessment of molecular criteria for species demarcation
Archives of Virology, 2004Co-Authors: M J Adams, John F. Antoniw, G. D. Foster, R. G. Milne, G. P. Martelli, A. A. Brunt, Thierry Candresse, M. Joseph, Claude M FauquetAbstract:Summary. The new Plant Virus family Flexiviridae is described. The family is named because its members have flexuous virions and it includes the existing genera AllexiVirus, CapilloVirus,CarlaVirus,FoveaVirus,PotexVirus,TrichoVirus andVitiVirus, plus the new genus MandariVirus together with some related Viruses not assigned to any genus. The family is justified from phylogenetic analyses of the polymerase and coat protein (CP) sequences. To help to define suitable molecular criteria for demarcation of species, a complete set of pairwise comparisons was made using the nucleotide (nt) and amino acid (aa) sequences of each fullysequenced gene from every available accession in the family. Based on the distributions and on inspection of the data, it was concluded that, as a general rule, distinct species have less than ca. 72% identical nt or 80% identical aa between their entire CP or replication protein genes.
Jose M Malpica - One of the best experts on this subject based on the ideXlab platform.
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variability and genetic structure of Plant Virus populations
Annual Review of Phytopathology, 2001Co-Authors: Fernando Garciaarenal, Aurora Fraile, Jose M MalpicaAbstract:▪ Abstract Populations of Plant Viruses, like all other living beings, are genetically heterogeneous, a property long recognized in Plant virology. Only recently have the processes resulting in genetic variation and diversity in Virus populations and genetic structure been analyzed quantitatively. The subject of this review is the analysis of genetic variation, its quantification in Plant Virus populations, and what factors and processes determine the genetic structure of these populations and its temporal change. The high potential for genetic variation in Plant Viruses, through either mutation or genetic exchange by recombination or reassortment of genomic segments, need not necessarily result in high diversity of Virus populations. Selection by factors such as the interaction of the Virus with host Plants and vectors and random genetic drift may in fact reduce genetic diversity in populations. There is evidence that negative selection results in Virus-encoded proteins being not more variable than those...
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variability and genetic structure of Plant Virus populations
Annual Review of Phytopathology, 2001Co-Authors: Fernando Garciaarenal, Aurora Fraile, Jose M MalpicaAbstract:Populations of Plant Viruses, like all other living beings, are genetically heterogeneous, a property long recognized in Plant virology. Only recently have the processes resulting in genetic variation and diversity in Virus populations and genetic structure been analyzed quantitatively. The subject of this review is the analysis of genetic variation, its quantification in Plant Virus populations, and what factors and processes determine the genetic structure of these populations and its temporal change. The high potential for genetic variation in Plant Viruses, through either mutation or genetic exchange by recombination or reassortment of genomic segments, need not necessarily result in high diversity of Virus populations. Selection by factors such as the interaction of the Virus with host Plants and vectors and random genetic drift may in fact reduce genetic diversity in populations. There is evidence that negative selection results in Virus-encoded proteins being not more variable than those of their hosts and vectors. Evidence suggests that small population diversity, and genetic stability, is the rule. Populations of Plant Viruses often consist of a few genetic variants and many infrequent variants. Their distribution may provide evidence of a population that is undifferentiated, differentiated by factors such as location, host Plant, or time, or that fluctuates randomly in composition, depending on the Virus.
Sourabh Shukla - One of the best experts on this subject based on the ideXlab platform.
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combination of Plant Virus nanoparticle based in situ vaccination with chemotherapy potentiates antitumor response
Nano Letters, 2017Co-Authors: Karin L Lee, Sourabh Shukla, Abner A Murray, Mee Rie Sheen, Ulrich Commandeur, Steven Fiering, Nicole F SteinmetzAbstract:Immunotherapeutics are gaining more traction in the armamentarium used to combat cancer. Specifically, in situ vaccination strategies have gained interest because of their ability to alter the tumor microenvironment to an antitumor state. Herein, we investigate whether flexuous Plant Virus-based nanoparticles formed by the potato Virus X (PVX) can be used as an immunotherapeutic for in situ vaccine monotherapy. We further developed dual chemo-immunotherapeutics by incorporating doxorubicin (DOX) into PVX yielding a dual-functional nanoparticle (PVX–DOX) or by coadministration of the two therapeutic regimes, PVX immunotherapy and DOX chemotherapy (PVX+DOX). In the context of B16F10 melanoma, PVX was able to elicit delayed tumor progression when administered as an intratumoral in situ vaccine. Furthermore, the coadministration of DOX via PVX+DOX enhanced the response of the PVX monotherapy through increased survival, which was also represented in the enhanced antitumor cytokine/chemokine profile stimulated ...
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serum albumin camouflage of Plant Virus based nanoparticles prevents their antibody recognition and enhances pharmacokinetics
Biomaterials, 2016Co-Authors: Andrzej S Pitek, Slater A Jameson, Frank A Veliz, Sourabh Shukla, Nicole F SteinmetzAbstract:Abstract Plant Virus-based nanoparticles (VNPs) are a novel class of nanocarriers with unique potential for biomedical applications. VNPs have many advantageous properties such as ease of manufacture and high degree of quality control. Their biocompatibility and biodegradability make them an attractive alternative to synthetic nanoparticles (NPs). Nevertheless, as with synthetic NPs, to be successful in drug delivery or imaging, the carriers need to overcome several biological barriers including innate immune recognition. Plasma opsonization can tag (V)NPs for clearance by the mononuclear phagocyte system (MPS), resulting in shortened circulation half lives and non-specific sequestration in non-targeted organs. PEG coatings have been traditionally used to ‘shield’ nanocarriers from immune surveillance. However, due to broad use of PEG in cosmetics and other industries, the prevalence of anti-PEG antibodies has been reported, which may limit the utility of PEGylation in nanomedicine. Alternative strategies are needed to tailor the in vivo properties of (Plant Virus-based) nanocarriers. We demonstrate the use of serum albumin (SA) as a viable alternative. SA conjugation to tobacco mosaic Virus (TMV)-based nanocarriers results in a ‘camouflage’ effect more effective than PEG coatings. SA-‘camouflaged’ TMV particles exhibit decreased antibody recognition, as well as enhanced pharmacokinetics in a Balb/C mouse model. Therefore, SA-coatings may provide an alternative and improved coating technique to yield (Plant Virus-based) NPs with improved in vivo properties enhancing drug delivery and molecular imaging.
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the protein corona of Plant Virus nanoparticles influences their dispersion properties cellular interactions and in vivo fates
Small, 2016Co-Authors: Andrzej S Pitek, Sourabh Shukla, Amy M Wen, Nicole F SteinmetzAbstract:Biomolecules in bodily fluids such as plasma can adsorb to the surface of nanoparticles and influence their biological properties. This phenomenon, known as the protein corona, is well established in the field of synthetic nanotechnology but has not been described in the context of Plant Virus nanoparticles (VNPs). The interaction between VNPs derived from Tobacco mosaic Virus (TMV) and plasma proteins is investigated, and it is found that the VNP protein corona is significantly less abundant compared to the corona of synthetic particles. The formed corona is dominated by complement proteins and immunoglobulins, the binding of which can be reduced by PEGylating the VNP surface. The impact of the VNP protein corona on molecular recognition and cell targeting in the context of cancer and thrombosis is investigated. A library of functionalized TMV rods with polyethylene glycol (PEG) and peptide ligands targeting integrins or fibrin(ogen) show different dispersion properties, cellular interactions, and in vivo fates depending on the properties of the protein corona, influencing target specificity, and non-specific scavenging by macrophages. Our results provide insight into the in vivo properties of VNPs and suggest that the protein corona effect should be considered during the development of efficacious, targeted VNP formulations.
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infusion of imaging and therapeutic molecules into the Plant Virus based carrier cowpea mosaic Virus cargo loading and delivery
Journal of Controlled Release, 2013Co-Authors: Ibrahim Yildiz, Sourabh Shukla, Karin L Lee, Kevin Chen, Nicole F SteinmetzAbstract:This work is focused on the development of a Plant Virus-based carrier system for cargo delivery, specifically 30nm-sized cowpea mosaic Virus (CPMV). Whereas previous reports described the engineering of CPMV through genetic or chemical modification, we report a non-covalent infusion technique that facilitates efficient cargo loading. Infusion and retention of 130-155 fluorescent dye molecules per CPMV using DAPI (4',6-diamidino-2-phenylindole dihydrochloride), propidium iodide (3,8-diamino-5-[3-(diethylmethylammonio)propyl]-6-phenylphenanthridinium diiodide), and acridine orange (3,6-bis(dimethylamino)acridinium chloride), as well as 140 copies of therapeutic payload proflavine (PF, acridine-3,6-diamine hydrochloride), is reported. Loading is achieved through interaction of the cargo with the CPMV's encapsidated RNA molecules. The loading mechanism is specific; empty RNA-free eCPMV nanoparticles could not be loaded. Cargo-infused CPMV nanoparticles remain chemically active, and surface lysine residues were covalent modified with dyes leading to the development of dual-functional CPMV carrier systems. We demonstrate cargo-delivery to a panel of cancer cells (cervical, breast, and colon): CPMV nanoparticles enter cells via the surface marker vimentin, the nanoparticles target the endolysosome, where the carrier is degraded and the cargo is released allowing imaging and/or cell killing. In conclusion, we demonstrate cargo-infusion and delivery to cells; the methods discussed provide a useful means for functionalization of CPMV toward its application as drug and/or contrast agent delivery vehicle.
