Rapid tumoritropic accumulation of systemically injected plateloid particles and their biodistribution

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Nanoparticles for cancer therapy and imaging are designed to accumulate in the diseased tissue by exploiting the Enhanced Permeability and Retention (EPR) effect. This limits their size to about 100 nm. Here, using intravital microscopy and elemental analysis, we compare the in vivo localization of particles with different geometries and demonstrate that plateloid particles preferentially accumulate within the tumor vasculature at unprecedented levels, independent of the EPR effect. In melanoma-bearing mice, 1000 x 400 nm plateloid particles adhered to the tumor vasculature at about 5% and 10% of the injected dose per gram organ (ID/g) for untargeted and RGD-targeted particles respectively, and exhibited the highest tumor-to-liver accumulation ratios (0.22 and 0.35). Smaller and larger plateloid particles, as well as cylindroid particles, were more extensively sequestered by the liver, spleen, and lungs. Plateloid particles appeared well-suited for taking advantage of hydrodynamic forces and interfacial interactions required for efficient tumoritropic accumulation, even without using specific targeting ligands. (c) 2011 Elsevier B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2012-02
Language
English
Article Type
Article
Keywords

POROUS SILICON MICROPARTICLES; HUMAN TUMOR XENOGRAFT; IN-VIVO; MACROMOLECULAR THERAPEUTICS; VASCULAR-PERMEABILITY; DELIVERY-SYSTEM; CANCER-THERAPY; DRUG-DELIVERY; SOLID TUMORS; BLOOD-FLOW

Citation

JOURNAL OF CONTROLLED RELEASE, v.158, no.1, pp.148 - 155

ISSN
0168-3659
DOI
10.1016/j.jconrel.2011.10.021
URI
http://hdl.handle.net/10203/96139
Appears in Collection
NT-Journal Papers(저널논문)
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