The Protein Corona of Plant Virus Nanoparticles Influences their Dispersion Properties, Cellular Interactions, and In Vivo Fates

Pitek, Andrzej S.; Wen, Amy M.; Shukla, Sourabh; Steinmetz, Nicole F.

doi:10.1002/smll.201502458

Cited by 76 publications

(74 citation statements)

References 59 publications

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“…Triplicates of sulfo-Cyanine5 azide (Cy5)-labeled TMV-RGD (300 nm long) were added at a concentration of 100,000 particles/cell and incubated for 3, 1.5, and 0.5 h at 37 °C, 5% CO 2 . The Cy5-TMV-RGD particles were synthesized and characterized as described by Pitek et al 27 Control experiments were conducted, in triplicate, with no particles present. Post incubation with TMV nanoparticles, cells were spun down at 500 g for 4 min.…”

Section: Experimental Methodsmentioning

confidence: 99%

Diffusion and Uptake of Tobacco Mosaic Virus as Therapeutic Carrier in Tumor Tissue: Effect of Nanoparticle Aspect Ratio

et al. 2016

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Nanoparticle-based technologies, including platforms derived from plant viruses, hold great promise for targeting and delivering cancer therapeutics to solid tumors by overcoming dose-limiting toxicities associated with chemotherapies. A growing body of data indicates advantageous margination and penetration properties of high aspect-ratio nanoparticles, which enhance payload delivery, resulting in increased efficacy. Our lab has demonstrated that elongated rod-shaped and filamentous macromolecular nucleoprotein assemblies from plant viruses have higher tissue diffusion rates than spherical particles. In this study, we developed a mathematical model to quantify diffusion and uptake of tobacco mosaic virus (TMV) in a spheroid system approximating a capillary-free segment of a solid tumor. Model simulations predict TMV concentration distribution with time in a tumor spheroid for different sizes and cell densities. From simulations of TMV concentration distribution, we can quantify the effect of TMV aspect ratio (e.g., nanorod length-to-width) with and without cellular uptake by modulated surface chemistry. This theoretical analysis can be applied to other viral or nonviral delivery systems to complement the experimental development of the next generation of nanotherapeutics.

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Section: Experimental Methodsmentioning

confidence: 99%

Diffusion and Uptake of Tobacco Mosaic Virus as Therapeutic Carrier in Tumor Tissue: Effect of Nanoparticle Aspect Ratio

et al. 2016

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“…Antibodies against TMV, therefore, may be prevalent in the human population. Indeed, we have previously found binding of immunoglobulins to TMV upon incubation in human plasma collected from random donors [45]. If antibodies are not already present, these are developed after repeat administration of TMV-based therapeutics.…”

Section: Resultsmentioning

confidence: 99%

“…In particular, SA coatings outperformed PEG coatings in terms of antibody evasion and pharmacokinetics, resulting in effective evasion from antibody recognition and 10-times increased circulation half-life of t 1/2 ~ 100 mins vs. the PEGylated TMV formulation. Macrophage uptake was reduced compared to ‘naked’ TMV but no differences were observed comparing SA- vs. PEG-coated TMV, indicating that antibody-mediated clearance is the dominating factor for the rapid plasma clearance of TMV (we have previously shown that the protein corona formed on ‘naked’ TMV in plasma consists of immunoglobulins [45]). To be effective for systemic and repeat administration, evasion of antibody surveillance is an important goal.…”

Section: Discussionmentioning

confidence: 99%

Serum albumin ‘camouflage’ of plant virus based nanoparticles prevents their antibody recognition and enhances pharmacokinetics

et al. 2016

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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. We demonstrate that 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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“…Animal studies will provide insight into the clearance and biodistribution of the particles, as well as the behavior of the particles in the presence of serum proteins, which will be important considerations for future translation. 31 …”

Section: Resultsmentioning

confidence: 99%

Utilizing Viral Nanoparticle/Dendron Hybrid Conjugates in Photodynamic Therapy for Dual Delivery to Macrophages and Cancer Cells

Wen¹,

Lee²,

Cao³

et al. 2016

Bioconjugate Chem.

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Photodynamic therapy (PDT) is a promising avenue for greater treatment efficacy of highly resistant and aggressive melanoma. Through photosensitizer attachment to nanoparticles, specificity of delivery can be conferred to further reduce potential side effects. While the main focus of PDT is the destruction of cancer cells, additional targeting of tumor-associated macrophages also present in the tumor microenvironment could further enhance treatment by eliminating their role in processes such as invasion, metastasis, and immunosuppression. In this study, we investigated PDT of macrophages and tumor cells through delivery using the natural noninfectious nanoparticle cowpea mosaic virus (CPMV), which has been shown to have specificity for the immunosuppressive subpopulation of macrophages and also targets cancer cells. We further explored conjugation of CPMV/dendron hybrids in order to improve the drug loading capacity of the nanocarrier. Overall, we demonstrated effective elimination of both macrophage and tumor cells at low micromolar concentrations of the photosensitizer when delivered with the CPMV bioconjugate, thereby potentially improving melanoma treatment.

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The Protein Corona of Plant Virus Nanoparticles Influences their Dispersion Properties, Cellular Interactions, and In Vivo Fates

Cited by 76 publications

References 59 publications

Diffusion and Uptake of Tobacco Mosaic Virus as Therapeutic Carrier in Tumor Tissue: Effect of Nanoparticle Aspect Ratio

Diffusion and Uptake of Tobacco Mosaic Virus as Therapeutic Carrier in Tumor Tissue: Effect of Nanoparticle Aspect Ratio

Serum albumin ‘camouflage’ of plant virus based nanoparticles prevents their antibody recognition and enhances pharmacokinetics

Utilizing Viral Nanoparticle/Dendron Hybrid Conjugates in Photodynamic Therapy for Dual Delivery to Macrophages and Cancer Cells

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