Development of Rous sarcoma Virus-like Particles Displaying hCC49 scFv for Specific Targeted Drug Delivery to Human Colon Carcinoma Cells

Kato, Tatsuya; Yui, Megumi; Deo, Vipin Kumar; Park, Enoch Y.

doi:10.1007/s11095-015-1730-2

Cited by 31 publications

(29 citation statements)

References 31 publications

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“…79 VLPs based on Rous sarcoma virus displaying the single chain fragment variable (scFv) antibody hcc49 were produced in silkworm larvae and loaded with DOX and demonstrated the ability to kill colon carcinoma cells in vitro . 80 Truncated hepatitis B virus core protein (tHBcAg) loaded with DOX and poly(acrylic acid) demonstrated a sustained drug release profile in vitro in colorectal cancer cells, leading to enhanced antitumor effects. 81 Again, the studies described here and the growing body of data in the literature support the further development and testing of virus-based drug carriers.…”

Section: Resultsmentioning

confidence: 99%

Physalis Mottle Virus-Like Particles as Nanocarriers for Imaging Reagents and Drugs

et al. 2017

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Platform technologies based on plant virus nano-particles (VNPs) and virus-like particles (VLPs) are attracting the attention of researchers and clinicians because the particles are biocompatible, biodegradable, noninfectious in mammals, and can readily be chemically and genetically engineered to carry imaging agents and drugs. When the Physalis mottle virus (PhMV) coat protein is expressed in Escherichia coli, the resulting VLPs are nearly identical to the viruses formed in vivo. Here, we isolated PhMV-derived VLPs from ClearColi cells and carried out external and internal surface modification with fluorophores using reactive lysine-N-hydroxysuccinimide ester and cysteine-maleimide chemistries, respectively. The uptake of dye-labeled particles was tested in a range of cancer cells and monitored by confocal microscopy and flow cytometry. VLPs labeled internally on cysteine residues were taken up with high efficiency by several cancer cell lines and were colocalized with the endolysosomal marker LAMP-1 within 6 h, whereas VLPs labeled externally on lysine residues were taken up with lower efficiency, probably reflecting differences in surface charge and the propensity to bind to the cell surface. The infusion of dye and drug molecules into the cavity of the VLPs revealed that the photosensitizer (PS), Zn-EpPor, and the drugs crystal violet, mitoxantrone (MTX), and doxorubicin (DOX) associated stably with the carrier via noncovalent interactions. We confirmed the cytotoxicity of the PS-PhMV and DOX-PhMV particles against prostate cancer, ovarian and breast cancer cell lines, respectively. Our results show that PhMV-derived VLPs provide a new platform technology for the delivery of imaging agents and drugs, with preferential uptake into cancer cells. These particles could therefore be developed as multifunctional tools for cancer diagnosis and therapy.

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Section: Resultsmentioning

confidence: 99%

Physalis Mottle Virus-Like Particles as Nanocarriers for Imaging Reagents and Drugs

et al. 2017

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“…7a-c), a known cytokine for therapy against cancers that plays an important role in the regulation of immune cells. 13 The interior of VLP is empty; therefore, we previously demonstrated that RSV VLPs can be packaged with drugs or dyes 17,18 , indicating that the chemotherapeutic drugs cisplatin and dacarbazine can be packaged into RSV VLP-rscFv-rhIL2 and that dual-functional chemotherapeutic agents can be created. In the case of RSV VLP-rscFv-rhIL2 having chemotherapeutic drugs, these drugs can also be specifically delivered to cancer cells expressing TAG-72, mitigating the side effects of chemotherapeutic 286 drugs.…”

Section: Discussionmentioning

confidence: 99%

“…VLP-rscFv-rhIL2s were produced in silkworm by the co-expression of the gag, rscFv and rhIL2 proteins using Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid. To display on the surface of RSV VLPs, rscFv and rhIL2 were anchored using glycophosphoinositol (GPI) 17 and hemagglutinin transmembrane region (HA-TM) 18 , respectively. Each of these anchors can be easily embedded in a lipid bilayer to display the proteins, but here we focus on simultaneously displaying two anchors.…”

Section: Introductionmentioning

confidence: 99%

Virus-Like Particles Displaying Recombinant Short-Chain Fragment Region and Interleukin 2 for Targeting Colon Cancer Tumors and Attracting Macrophages

Deo

Kato

Park

2016

Journal of Pharmaceutical Sciences

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Functionalized virus-like particles (VLPs) can target with specificity as drug delivery systems and can attract macrophages for the destruction of cancer cells. Here, the group antigen capsid protein from the Rous sarcoma virus was used to prepare VLPs, functionalized by displaying glycol-inositol phosphate-anchored recombinant single chain fragment variable (rscFv) and hemagglutinin transmembrane region anchored recombinant human interleukin-2 (rhIL2) (designated as VLP-rscFv-rhIL2s) in silkworms. The rscFv specifically binds the tumor-associated glycoprotein 72 that is expressed at the surface of colon cancer cells. VLP-rscFv-rhIL2 was affinity purified and had a smooth particle size with a diameter of 50 nm. Calcein-AM-packaged VLP-rscFv-rhIL2s successfully targeted cancer cells as a model for drug delivery system. VLP-rscFv-rhIL2 bound with colon cancer cells that attracted macrophages (human monocytic cell line-1 cells) in chemotaxis chamber assays compared with negative controls. The macrophages secreted tumor necrosis factor-α, a cytokine that is necessary to destroy cancer cells. These results demonstrate the potential of VLP-rscFv-rhIL2 as an intelligent nano biomaterial that is capable of attracting macrophages.

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“…Therefore, VLPs can be used to deliver therapeutic cargoes to tumours. Similarly, Rous sarcoma VLPs could deliver drugs to colon carcinoma cells [42] and rabbit hemorrhagic disease virus VLPs could deliver gp33 peptide and inhibit the growth of Lewis’ lung carcinoma tumours [43]. Although virosomes and VLPs have proven to be successful vaccines with a potentially improved safety profile, they might not be suitable for all patients as some cancers evolved mechanisms that render them refractory to immunization strategies.…”

Section: A Viral Strategymentioning

confidence: 99%

Taking a Stab at Cancer; Oncolytic Virus-Mediated Anti-Cancer Vaccination Strategies

2017

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Vaccines have classically been used for disease prevention. Modern clinical vaccines are continuously being developed for both traditional use as well as for new applications. Typically thought of in terms of infectious disease control, vaccination approaches can alternatively be adapted as a cancer therapy. Vaccines targeting cancer antigens can be used to induce anti-tumour immunity and have demonstrated therapeutic efficacy both pre-clinically and clinically. Various approaches now exist and further establish the tremendous potential and adaptability of anti-cancer vaccination. Classical strategies include ex vivo-loaded immune cells, RNA- or DNA-based vaccines and tumour cell lysates. Recent oncolytic virus development has resulted in a surge of novel viruses engineered to induce powerful tumour-specific immune responses. In addition to their use as cancer vaccines, oncolytic viruses have the added benefit of being directly cytolytic to cancer cells and thus promote antigen recognition within a highly immune-stimulating tumour microenvironment. While oncolytic viruses are perfectly equipped for efficient immunization, this complicates their use upon previous exposure. Indeed, the host’s anti-viral counter-attacks often impair multiple-dosing regimens. In this review we will focus on the use of oncolytic viruses for anti-tumour vaccination. We will explore different strategies as well as ways to circumvent some of their limitations.

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Development of Rous sarcoma Virus-like Particles Displaying hCC49 scFv for Specific Targeted Drug Delivery to Human Colon Carcinoma Cells

Abstract: These results showed that hCC49 scFv-displaying RSV VLPs from silkworm larvae offered specific drug delivery to colon carcinoma cells in vitro. This scFv-displaying enveloped VLP system could be applied to drug and gene delivery to other target cells.

Cited by 31 publications

References 31 publications

Physalis Mottle Virus-Like Particles as Nanocarriers for Imaging Reagents and Drugs

Physalis Mottle Virus-Like Particles as Nanocarriers for Imaging Reagents and Drugs

Virus-Like Particles Displaying Recombinant Short-Chain Fragment Region and Interleukin 2 for Targeting Colon Cancer Tumors and Attracting Macrophages

Taking a Stab at Cancer; Oncolytic Virus-Mediated Anti-Cancer Vaccination Strategies

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