Supramolecular Nanofibrillar Thermoreversible Hydrogel for Growth and Release of Cancer Spheroids

Abstract

Growth of three-dimensional cancer spheroids (CSs) in man-made hydrogels mimicking natural extracellular matrix is an important and challenging task. Herein, we report on a supramolecular temperature-responsive hydrogel designed for the growth and subsequent release of CSs. A filamentous hydrogel was formed at 37 °C from an aqueous suspension of cellulose nanocrystals surface-functionalized with temperature-responsive polymer molecules. The encapsulation of cells in the hydrogel enabled effective growth of CSs with dimensions determined by the concentration of cellulose nanocrystals in the hydrogel. On demand release of CSs without loss of cell viability and spheroid integrity was achieved upon hydrogel cooling. The tumorigenic properties of the released CSs were examined by encapsulating and re-growing them in fibrin hydrogel. The results in this work can be used in fundamental cancer research and in cancer drug screening.

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.…”

Chemical Institute of Canada and Canadian Society for Chemistry Awards

“…Kumacheva's research is focused on soft matter, in particular polymer materials science, nanoscience, polymers in biological systems, and microfluidics. Her report on a supramolecular nanofibrillar thermoreversible hydrogel is published in this issue …”

The Construction and Application of Three‐Dimensional Biomaterials

“…Ideally, the generated cell spheroids are expected to release in some circumstances. It was reported that a kind of nanofibrillar thermoreversible hydrogel was formed by temperature‐responsive polymer poly( N ‐isopropylacrylamide) (PNIPAM) grafted cellulose nanocrystals (CNCs) . Cancer cells were encapsulated in this hydrogel and gradually formed spheroids at 37 °C, which could be released by cooling‐induced hydrogel liquefaction (Figure 7b).…”

“…b) Cancer spheroids formed and released on demand a thermoreversible hydrogel. Reproduced with permission . Copyright 2016, Wiley‐VCH.…”