W.J. Mulder

Publications (5)10.77 Total impact

• Article: Multifunctional nanoemulsion platform for imaging guided therapy evaluated in experimental cancer

  A. Gianella, P. A. Jarzyna, V. Mani, S. Ramachandran, C. Calcagno, J. Tang, B. Kann, W. J. Dijk, V. L. Thijssen, A. W. Griffioen, G. Storm, Z. A. Fayad, W. J. Mulder
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  ABSTRACT: Nanoparticle applications in medicine have seen a tremendous growth in the past decade. In addition to their drug targeting application and their ability to improve bioavailability of drugs, nanoparticles can be designed to allow their detection with a variety of imaging methodologies. In the current study, we developed a multimodal nanoparticle platform to enable imaging guided therapy, which was evaluated in a colon cancer mouse model. This "theranostic" platform is based on oil-in-water nanoemulsions and carries iron oxide nanocrystals for MRI, the fluorescent dye Cy7 for NIRF imaging, and the hydrophobic glucocorticoid prednisolone acetate valerate (PAV) for therapeutic purposes. Angiogenesis-targeted nanoemulsions functionalized with alphavbeta(3)-specific RGD peptides were evaluated, as well. When subcutaneous tumors were palpable, the nanoemulsions were administered at a dose of 30 mg of FeO/kg and 10 mg of PAV/kg. MRI and NIRF imaging showed significant nanoparticle accumulation in the tumors, while tumor growth profiles revealed a potent inhibitory effect in all of the PAV nanoemulsion-treated animals as compared to the ones treated with control nanoemulsions, the free drug, or saline. This study demonstrated that our nanoemulsions, when loaded with PAV, iron oxide nanocrystals, and Cy7, represent a flexible and unique theranostic nanoparticle platform that can be applied for imaging guided therapy of cancer.
  ACS Nano 05/2011; 5(6):4422-33. · 10.77 Impact Factor
• Article: Paramagnetic and fluorescent liposomes for target-specific imaging and therapy of tumor angiogenesis

  G.J. Strijkers, E. Kluza, G.A.F. van Tilborg, D W van der Schaft, A W Griffioen, W.J. Mulder, K Nicolay
• Article: RGD peptide functionalized and reconstituted high-density lipoprotein nanoparticles as a versatile and multimodal tumor targeting molecular imaging probe

  W. Chen, P.A. Jarzyna, G.A.F. van Tilborg, V.A. Nguyen, D.P. Cormode, A. van Klink, A W Griffioen, G.J. Randolph, E A Fisher, W.J. Mulder, Z A Fayad
• Article: Annexin A5-conjugated quantum dots with a paramagnetic lipidic coating for the multimodal detection of apoptotic cells

  G. A. van Tilborg, W. J. Mulder, P. T. Chin, G. Storm, C. P. Reutelingsperger, K. Nicolay, G. J. Strijkers
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  ABSTRACT: Apoptosis, or programmed cell death, plays an important role in the etiology of a variety of diseases, including cancer. Visualization of apoptosis would allow both early detection of therapy efficiency and evaluation of disease progression. To that aim we developed a novel annexin A5-conjugated bimodal nanoparticle. The nanoparticle is composed of a quantum dot that is encapsulated in a paramagnetic micelle to enable its use both for optical imaging and MRI. Multiple recombinant human annexin A5 protein molecules were covalently coupled to the nanoparticle for targeting. In this study the specificity of the annexin A5-conjugated nanoparticles for apoptotic cells was demonstrated both with fluorescence microscopy and MRI, which confirms its potential for the detection of apoptosis with both imaging modalities in vivo.
  Bioconjugate chemistry. 17(4):865-8.
• Article: Improved magnetic resonance molecular imaging of tumor angiogenesis by avidin-induced clearance of nonbound bimodal liposomes

  G. A. van Tilborg, W. J. Mulder, D. W. van der Schaft, C. P. Reutelingsperger, A. W. Griffioen, G. J. Strijkers, K. Nicolay
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  ABSTRACT: Angiogenic, that is, newly formed, blood vessels play an important role in tumor growth and metastasis and are a potential target for tumor treatment. In previous studies, the alpha(v)beta(3) integrin, which is strongly expressed in angiogenic vessels, has been used as a target for Arg-Gly-Asp (RGD)-functionalized nanoparticulate contrast agents for magnetic resonance imaging-based visualization of angiogenesis. In the present study, the target-to-background ratio was increased by diminishing the nonspecific contrast enhancement originating from contrast material present in the blood pool. This was accomplished by the use of a so-called avidin chase, which allowed rapid clearance of non-bound paramagnetic RGD-biotin-liposomes from the blood circulation. C57BL/6 mice, bearing a B16F10 mouse melanoma, received RGD-functionalized or untargeted biotin-liposomes, which was followed by avidin infusion or no infusion. Precontrast, postcontrast, and postavidin T(1)-weighted magnetic resonance images were acquired at 6.3 T. Postcontrast images showed similar percentages of contrast-enhanced pixels in the tumors of mice that received RGD-biotin-liposomes and biotin-liposomes. Post avidin infusion this percentage rapidly decreased to precontrast levels for biotin-liposomes, whereas a significant amount of contrast-enhanced pixels remained present for RGD-biotin-liposomes. These results showed that besides target-associated contrast agent, the circulating contrast agent contributed significantly to the contrast enhancement as well. Ex vivo fluorescence microscopy confirmed association of the RGD-biotin-liposomes to tumor endothelial cells both with and without avidin infusion, whereas biotin-liposomes were predominantly found within the vessel lumen. The clearance methodology presented in this study successfully enhanced the specificity of molecular magnetic resonance imaging and opens exciting possibilities for studying detection limits and targeting kinetics of site-directed contrast agents in vivo.
  Neoplasia. 10(12):1459-69.