Cationic Conjugated Polymer/Fluoresceinamine-Hyaluronan Complex for Sensitive Fluorescence Detection of CD44 and Tumor-Targeted Cell Imaging

Abstract

Simple, rapid, and sensitive detection of CD44 is of paramount importance since it plays pivotal roles in tumor initiation, growth and metastasis. Herein, we describe a novel method for sensitive, visual and facile fluorescence detection of CD44 and CD44-mediated cancer cell imaging, using a probe based on cationic conjugated polymer (CCP)-PFEP and fluoresceinamine-hyaluronan (FA-HA). HA is an anionic natural glycosaminoglycan that can specifically bind to the overexpressed CD44 on various kinds of cancer cells. PFEP and FA-HA formed a complex through electronic interactions, resulting in a highly efficient fluorescence resonance energy transfer (FRET) from PFEP to FA-HA; moreover, the efficiencies of FRET correlated with the concentrations of CD44 because the specific binding of HA-CD44 would separate FA-HA away from PFEP. This method did not require laborious and expensive dual-labeling or protein-labeling needed in previously reported detection methods of CD44. Just mix the sample and test solution containing the PFEP/FA-HA complex, and the results allowed naked-eye detection by observing fluorescent color of solutions with the assistance of a UV lamp. Most importantly, the use of a conjugated polymer with excellent amplification property as well as the specific binding of HA-CD44 endowed this method with high sensitivity and specificity, making it applicable for reliable quantitative detection of CD44. Furthermore, the PFEP/FA-HA complex formed nanoparticles in aqueous solution, and the nanoparticles can be selectively taken up by MCF-7 cells (cancer cell) through the HA-CD44 interaction, thereby giving rise to a dual-color tumor-targeted imaging probe with good photostability. The development of this fluorescent probe showed promising potential to make a reliable and routine method available for early diagnosis of cancer.

Supramolecular Prodrug Nanovectors for Active Tumor Targeting and Combination Immunotherapy of Colorectal Cancer

“…CD44 is endogenously expressed in low levels in normal tissues, which is highly expressed in certain types of tumor cells including colorectal cancer. [ 44,45 ] The prodrug nanovectors could passively accumulate at the tumor site through the leaky structure of the tumor‐associated blood vessels. Upon binding with CD44 on the surface of tumor cells, the nanoparticles could be internalized with the tumor cells via CD44–HA interaction.…”

Redox-responsive hyaluronic acid-functionalized graphene oxide nanosheets for targeted delivery of water-insoluble cancer drugs

“…The cytotoxicity of NGO-SS-HA against cells was measured using the CCK-8 assay. A549 and HELF cells were seeded into 96-well cell culture plates at 1×10 4 /well for 24 hours and incubated with NGO-SS-HA at various concentrations for another 24, 48, and 72 hours. Next, the absorbance of each well was measured at 450 nm with a microplate reader (Tecan, Männedorf, Switzerland).…”

“…Moreover, it can also specifically bind the cluster determinant 44 (CD44) receptor, which is overexpressed on the surface of various tumor cells. [23][24][25] HA function not only improves the stability of GO in PBS and cell medium but also enhances the uptake of GO by CD44 receptor-overexpressing cells via the specific interaction between the CD44 receptor and HA.…”

A green and facile method for the preparation of a pH-responsive alginate nanogel for subcellular delivery of doxorubicin

“…27 Plain nanogel (pH-AN) was prepared following the above procedure without DOX involved. The solution of doxorubicin hydrochloride (4.0 mg/mL) was added dropwise to the stirred aqueous solution with sonication for 30 min to form a DOX-containing SA solution.…”