Abstract
This paper reports on the development of tumor-specific gold nanoparticles (AuNPs) as theranostic tools intended for target accumulation and the detection of tumor angiogenesis via optical imaging (OI) before therapy is performed, being initiated via an external X-ray irradiation source. The AuNPs were decorated with a near-infrared dye, and RGD peptides as the tumor targeting vector for αvβ3-integrin, which is overexpressed in tissue with high tumor angiogenesis. The AuNPs were evaluated in an optical imaging setting in vitro and in vivo exhibiting favorable diagnostic properties with regards to tumor cell accumulation, biodistribution, and clearance. Furthermore, the therapeutic properties of the AuNPs were evaluated in vitro on pUC19 DNA and on A431 cells concerning acute and long-term toxicity, indicating that these AuNPs could be useful as radiosensitizers in therapeutic concepts in the future.
Highlights
In recent years, gold nanoparticles (AuNPs) have gained serious attention since their first use as radioactive 198 Au-nanocolloid in the early 1950s for nanobrachytherapy [1,2,3].Since the focus has shifted to the development of ultra-small target-specific AuNPs with a very narrow size distribution and, tailored shapes for use in various imaging modalities such as CT [4], Raman [5], or photoacoustic imaging [6]
Growing malignant tumors continuously requires and for this purpose themaligintegrin tumors continuously requires angiogenesis, and for this purpose the integrin αvβ3 is αnant v β3 is overexpressed
Αv β3 is preferentially expressed in tumor angiogenesis vβ3 is preferentially expressed in tumor angiogenesis and is overexpressed
Summary
Gold nanoparticles (AuNPs) have gained serious attention since their first use as radioactive 198 Au-nanocolloid in the early 1950s for nanobrachytherapy [1,2,3]. The focus has shifted to the development of ultra-small target-specific AuNPs with a very narrow size distribution and, tailored shapes for use in various imaging modalities such as CT [4], Raman [5], or photoacoustic imaging [6]. On the one hand AuNPs represent a perfect platform for multimerization of target-specific effectors on their surface and on the other hand they offer the possibility of detection using multimodal imaging techniques by surface modification [7], as well as for theranostic purposes [8,9,10,11]. The development of methods for the synthesis of ultrasmall (
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