title: Rapid tumoritropic accumulation of systemically injected plateloid particles and their biodistribution.
abstract: 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 100nm. 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, 1000×400nm 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.
authors: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave, Houston, TX 77030, USA. avandeven@tmhs.org
authors: Anne L
authors: AL
authors: van de Ven
authors: Pilhan
authors: P
authors: Kim
authors: O'Hara
authors: O
authors: Haley
authors: Jean R
authors: JR
authors: Fakhoury
authors: Giulia
authors: G
authors: Adriani
authors: Jeffrey
authors: J
authors: Schmulen
authors: Padraig
authors: P
authors: Moloney
authors: Fazle
authors: F
authors: Hussain
authors: Mauro
authors: M
authors: Ferrari
authors: Xuewu
authors: X
authors: Liu
authors: Seok-Hyun
authors: SH
authors: Yun
authors: Paolo
authors: P
authors: Decuzzi
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D042787:Receptor, TIE-2; D012825:Silicon / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D049452:Green Fluorescent Proteins; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse; D012825:Silicon