A Dendron‐Based Fluorescence Turn‐On Probe for Tumor Detection

Abstract

Specifically amplifying the emission signals of optical probes in tumors is an effective way to improve the tumor-imagings ensitivity and contrast. In this paper,t he first case of dendron-based fluorescencet urn-on probes mediated by aF çrster resonance energy transfer (FRET) mechanism is reported. Dendrons up to the fourth generation with ah ydrophilic oligo(ethyleneg lycol)s caffold are synthesized by as olid-phase synthesis strategy,a nd show precise and defect-free chemical structures.T oc onstruct the fluorescence turn-on probe,o ne Cy5.5 moleculei sc onjugated to the focal of aG 3d endron through ar obust linkage and eight Black Hole Quencher3(BHQ-3) molecules are conjugatedt oi ts periphery through aP EG chainb earing ar e-ductivelyc leavable disulfidel inkage.B yi nv itro and in vivo experiments, it is demonstrated that the fluorescence of the dendron-based probec an be activated effectively and rapidly in the reductivee nvironments of tumor cellsa nd tissues, and the probe thuse xhibits amplified tumor signals and weak normalt issue signals.C ompared with the reported nanoscale turn-on probes, the dendron-based probe has several significant advantages, such as well-definedc hemical structure, precisely controllable fluorophore/quencher conjugations ites and ratio, desirable chemical stability,a nd reproducible pharmacokinetic and pharmacological profiles, and is very promising in tumor detection.

In vivo quantitative FRET small animal imaging: Intensity versus lifetime-based FRET

“…Extending FRET assays to in vivo noninvasive “macroscopy” is one of the last frontiers of FRET imaging. Recently, in vivo FRET imaging approaches have been implemented to measure nanoparticle drug delivery and release, drug-target engagement, and dynamic probe uptake or biosensor-based signaling in various preclinical animal models ( 8 , 9 , 34 , 35 , 36 , 37 , 38 , 39 ). A major issue preventing full application of FRET into small animal imaging is the need to red-shift FRET into the NIR range to reduce absorption and minimize autofluorescence, as well as to increase depth of penetration in thick tissues ( 40 ).…”

Phenylboronic acid-modified nanoscale multi-arm polymers for tumor-targeted therapy

“…16,17 Typically, unimolecular micelles, water-soluble dendrimers and cylindrical polymer brushes can be considered as UPNs. [18][19][20] UPNs can overcome the shortcomings of polymeric nanoassemblies because their good stability and designable drug conjugation ensure controllable drug release, and their well-defined structures impart batch-to-batch reproducible biological properties. However, UPNs generally suffer from complicated synthesis procedures, especially those for dendrimers and cylindrical polymer brushes.…”

An Orthogonal Protection Strategy for Synthesizing Scaffold-Modifiable Dendrons and Their Application in Drug Delivery

“…Dendrimers and dendrons are two types of monodisperse dendritic polymers. Dendrons can be looked as the wedge-shaped units of dendrimers. − Both dendrimers and dendrons have intriguing structural characteristics, such as a well-defined and widely tunable chemical structure, highly branched topology, nanoscale size, globular shape, abundant peripheral groups and available internal cavities, etc., which make them very promising in biomedical applications, for example, as nanocarriers for drugs or imaging contrast agents. − Their precisely controllable and widely tunable chemical structure not only ensures perfectly reproducible pharmacokinetic and pharmacological profiles but also renders versatile and tailorable biological functionalities . Their abundant groups and large internal cavities provide plenty of sites for drug loading.…”