Tunable immunonanoparticle binding to cancer cells: thermodynamic analysis of targeted drug delivery vehicles

Ho, Karyn; Lapitsky, Yakov; Shi, Meng; Shoichet, Molly S.

doi:10.1039/b814204a

Cited by 27 publications

(16 citation statements)

References 34 publications

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“…Although multivalent interactions between a NP and the targeted cell surface can significantly enhance the avidity of a NP-cell surface interaction, the decision to engineer multivalency into a NP formulation still requires consideration of NP size, ligand density, ligand size and the density/distribution of receptors on the targeted cell surface [160].…”

Section: Optimization Of Ligand Density and Distributionmentioning

confidence: 99%

Guiding Principles in The Design of Ligand-Targeted Nanomedicines

2014

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Medicines for the treatment of most human pathologies are encumbered by unwanted side effects that arise from the deposition of an effective drug into the wrong tissues. The logical remedy for these undesirable properties involves selective targeting of the therapeutic agent to pathologic cells, thereby avoiding collateral toxicity to healthy cells. Since significant advantages can also accrue by incorporating a therapeutic or imaging agent into a nanoparticle, many laboratories are now combining both benefits into a single formulation. This review will focus on the major guiding principles in the design of ligand-targeted nanoparticles, including optimization of their chemical and physical properties, selection of the ideal targeting ligand, engineering of the appropriate surface passivation and linker strategies to achieve selective delivery of the entrapped cargo to the desired diseased cell.

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Section: Optimization Of Ligand Density and Distributionmentioning

confidence: 99%

Guiding Principles in The Design of Ligand-Targeted Nanomedicines

2014

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“…Haun and Hammer [43] investigated the kinetic rate constants of attachment and detachment of 210 nm nanocarriers as a function of receptor density, ligand density on surface, and flow shear rate, and identified a time dependence of the detachment rate due to multivalent binding. Ho et al [123] studied the effect of antibody surface coverage on equilibrium binding constants by measuring fractional coverage of bound nanocarriers (80 nm in diameter) as a function of carrier concentrations; by fitting their experimental data, they observed linear dependence of K α on antibody surface coverage, leading them to conclude that the system was dominated by monovalent interactions. Immunotargeting of liposomes to activated vascular endothelial cells has been advocated as a strategy for site-selective delivery in the cardiovascular system by Spragg et al [34].…”

Section: Endothelial Target Moleculesmentioning

confidence: 99%

“…Using this method, the authors were able to quantify binding strength, allowing them to better understand whether Nanocarriers were bound by monovalent or multivalent interactions. The binding data for each formulation were fitted to Langmuir isotherms, and based on the theory presented, it was concluded that the system studied behaved in a manner consistent with monovalent binding [123]. Liu et al [89] developed a computational model to calculate the absolute binding affinities between functionalized nanocarriers and the endothelial cell surface.…”

Section: Endothelial Target Moleculesmentioning

confidence: 99%

Dynamic Factors Controlling Targeting Nanocarriers to Vascular Endothelium

Muzykantov¹,

Radhakrishnan²,

Eckmann³

2012

CDM

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Endothelium lining luminal surface of blood vessels is the key target and barrier for vascular drug delivery. Nanocarriers coated with antibodies or affinity peptides that bind specifically to endothelial surface determinants provide targeted delivery of therapeutic cargoes to these cells. Endothelial targeting consists of several phases including circulation in the bloodstream, anchoring on the endothelial surface and, in some cases, intracellular uptake and trafficking of the internalized materials. Dynamic parameters of the vasculature including the blood hydrodynamics as well as surface density, accessibility, membrane mobility and clustering of target determinants modulate these phases of the targeting, especially anchoring to endothelium. Further, such controlled parameters of design of drug nanocarriers as affinity, surface density and epitope specificity of targeting antibodies, carrier size and shape also modulate endothelial targeting and resultant sub-cellular addressing. This article reviews experimental and computational approaches for analysis of factors modulating targeting nanocarriers to the endothelial cells.

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“…HER-2 targeting has been achieved by targeted nanoparticles as well as fluorophore-conjugated antibodies [8][9][10][11][12][13]. Our nanoparticle formulation provides a new approach which has proven to effectively target and selectively label ovarian cancer cells with high-HER-2 expression levels.…”

Section: Introductionmentioning

confidence: 98%

Targeted imaging of ovarian cancer cells using viral nanoparticles doped with indocyanine green

et al. 2013

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Our group has constructed a new type of viral nanoparticles (VNPs) from genome-depleted plant infecting brome mosaic virus (BMV) that encapsulates the FDA-approved near infrared (NIR) indocyanine green (ICG) [1]. We refer to these VNPs as optical viral ghosts (OVGs) since the constructs lack the genomic content of wild-type BMV. One of our areas of interest is the application of OVGs for real-time intraoperative NIR fluorescence imaging of small peritoneal ovarian tumor nodules. We target human epidermal growth factor receptor-2 (HER-2) expression in ovarian cancer as a biomarker associated with ovarian cancer, since its over-expression is linked to the disease's progression to death. We functionalize the OVGs with anti-HER-2 monoclonal antibodies using reductive amination methods. We used fluorescence imaging to visualize the SKOV-3 cells (high HER-2 expression) after incubation with free ICG, OVGs, and functionalized OVGs. Our results suggest the possibility of using anti-HER2 conjugated OVGs in conjunction with cytoreductive surgery to detect small tumor nodules (<5cm) which currently are not excised during surgery.

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Tunable immunonanoparticle binding to cancer cells: thermodynamic analysis of targeted drug delivery vehicles

Cited by 27 publications

References 34 publications

Guiding Principles in The Design of Ligand-Targeted Nanomedicines

Guiding Principles in The Design of Ligand-Targeted Nanomedicines

Dynamic Factors Controlling Targeting Nanocarriers to Vascular Endothelium

Targeted imaging of ovarian cancer cells using viral nanoparticles doped with indocyanine green

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