Fluorescent nanoprobes as a biomarker for increased vascular permeability: implications in diagnosis and treatment of cancer and inflammation.
This article describes the use of a fluorescent nanoprobe as a functional biomarker for the identification of increased vascular permeability in cancer/arthritis disease models. Synthesis of the fluorescent nanoprobe was achieved by passive loading of a fluorophore inside the nanoparticle using thin film hydration method. The outer layer of the nanoprobe was decorated with poly(ethylene glycol) arms to increase the bioavailability of the fluorophore. Stability studies of the nanoprobe showed that the particles were stable up to 70 days. The uptake and internalization of the fluorescent nanoprobe inside target cells was confirmed by fluorescence microscopy studies. Co-localization of the probe with the target tissue in vivo was unambiguously identified using intravital microscopy. Results from in vivo imaging studies showed that the particles had a long half-life in the circulation and passively targeted tumor or arthritic tissue. The increased and specific uptake of the fluorescent nanoprobe in tumor/arthritic tissue is attributed to an enhanced permeation and retention (EPR) effect. Use of an optical method to validate anti-inflammatory drugs in an arthritis disease model is demonstrated in this study. In general, this methodology could be used for detection of leaky vasculature in different pathological states.
Sandanaraj
Britto S
BS
Department of Autoimmunity, Novartis Institutes for Biomedical Research, Basel, Switzerland. sandanaraj.selvaraj@novartis.com
Gremlich
Hans-Ulrich
HU
Kneuer
Rainer
R
Dawson
Janet
J
Wacha
Stefan
S
D000818:Animals; D001168:Arthritis / Q000378:metabolism / Q000473:pathology; D001682:Biological Availability; D015415:Biomarkers / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology*; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000378:metabolism; D006207:Half-Life; D007249:Inflammation / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D049329:Nanostructures / Q000737:chemistry; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D005456:Fluorescent Dyes