Functionalization of Cellulose Nanocrystals with PEG-Metal-Chelating Block Copolymers via Controlled Conjugation in Aqueous Media

Abstract

Elongated nanoparticles have recently been shown to have distinct advantages over their spherical counterparts in drug delivery applications. Cellulose nanocrystals (CNCs) have rodlike shapes in nature and have demonstrated biocompatibility in a variety of mammalian cell lines. In this report, CNCs are put forward as a modular platform for the production of multifunctional rod-shaped nanoparticles for cancer imaging and therapy. For the first time, PEGylated metal-chelating polymers containing diethylenetriaminepentaacetic acid (DTPA) (i.e., mPEG-PGlu(DPTA)18-HyNic and PEG-PGlu(DPTA)25-HyNic) are conjugated to CNCs to enable the chelation of radionuclides for diagnostic and therapeutic applications. The entire conjugation is based on UV/vis-quantifiable bis-aryl hydrazone-bond formation, which allows direct quantification of the polymers grafted onto the CNCs. Moreover, it has been shown that the mean number of polymers grafted per CNC could be controlled. The CNCs are also fluorescently labeled with rhodamine and Alexa Fluor 488 by embedding the probes in the polymer corona. Preliminary evaluation in a human ovarian cancer cell line (HEYA8) demonstrated that these CNCs are nontoxic and their penetration properties can be readily assessed in multicellular tumor spheroids (MCTSs) by optical imaging. These findings provide support for biomedical applications of CNCs, and further in vitro and in vivo studies are warranted to evaluate their potential as imaging and therapeutic agents for cancer treatment.

Chiral Carbon Dots Synthesized on Cellulose Nanocrystals

“…There is a growing interest in using CNCs in nanomedicine, due to their biocompatibility, as well as their asymmetric (rod‐like) shape facilitating prolonged blood circulation time and possible cellular uptake . Furthermore, the hydroxyl groups on the CNCs surface are amenable for attachment of polymer molecules or imaging and therapeutic agents . Since C‐dot/CNC NPs can be used as biotags for labeling, sensing, and therapeutics, we examined their biocompatibility by culturing MCF‐7 breast cancer cells for 24 and 48 h in suspensions of hybrid NPs with concentrations from 0.00001 to 0.1 wt% in cell culture media.…”

“…Since C‐dot/CNC NPs can be used as biotags for labeling, sensing, and therapeutics, we examined their biocompatibility by culturing MCF‐7 breast cancer cells for 24 and 48 h in suspensions of hybrid NPs with concentrations from 0.00001 to 0.1 wt% in cell culture media. Notably, the highest tested concentration was at least, tenfold higher than the highest concentration tested for biocompatibility of composite CNC NPs . In the control experiment, the cells were cultured in the cell culture media without exposure to C‐dot/CNC NPs.…”

Colloidal Behavior of Cellulose Nanocrystals Grafted with Poly(2-alkyl-2-oxazoline)s

“…Preliminary evaluations have demonstrated that PEGylated CNCs are nontoxic for human ovarian cancer cell line (HEYA8). 34 Also, poly(2-aminoethylmethacrylate)- g -CNC toxicity was evaluated against mouse monocyte cells (J774A1) and human breast adenocarcinoma cells (MCF-7). 35 Even if no cytotoxicity to J774A1 cells was observed, an unexpected increase in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction was observed, requiring further investigations and demonstrating that such evaluations must be performed carefully case by case.…”

Actuation of Three‐Dimensional‐Printed Nanocolloidal Hydrogel with Structural Anisotropy

“…Covalent Attachment of Fluorescein Isothiocyanate to Cellulose Nanocrystals: The surface of CNCs was chemically modified with FITC dye, as described elsewhere. [43] Briefly, epichlorohydrin (5.8 mL, 0.28 mol g −1 CNC) was added to the mixture of 10 mL of 2.65 wt% of CNC suspension with 25 mL of 1 m NaOH (aq). The reaction mixture was stirred at 60 °C for 1 h, centrifuged (4000 × g for 10 min), and diluted with water, until the pH = 12 was reached (pH meter, Mettler Toledo).…”