Organ Distribution and Bone Tropism of Cellulose Nanocrystals in Living Mice

Abstract

Their physicochemical properties and relatively low cost make cellulose nanocrystals (CNCs) a potential candidate for future large-scale production in many fields including nanomedicine. Prior to a sustained and responsible development as theranostic agents, robust and reliable data concerning their safety, biocompatibility, and tissue distribution should be provided. In the present study, CNCs were extracted from Whatman filters functionalized with a fluorescent dye, and their interaction with living organisms has been thoroughly assessed. Our experimental evidence demonstrated that CNCs (1) are well tolerated by healthy mice after systemic injection; (2) are rapidly excreted, thus avoiding bioaccumulation in filter organs such as the kidneys and liver; (3) transiently migrate in bones; and (4) are able to penetrate in the cytoplasm of cancer cells without inducing material-related detrimental effects in terms of cell survival. Our results strongly suggest that the peculiar tropism to the bones is due to the chemical interaction between the Ca(2+) of the bone matrix and the active surface of negatively-charged CNCs. This feature, together with the ability to penetrate cancer cells, makes CNCs a potential nanodevice for theranostics in bone tumors.

Enhanced Mechanical Properties in Cellulose Nanocrystal–Poly(oligoethylene glycol methacrylate) Injectable Nanocomposite Hydrogels through Control of Physical and Chemical Cross-Linking

“…27,28 Based on their demonstrated low cytotoxicity [29][30][31][32][33][34][35] they have also recently gained interest in biomedical applications including tissue engineering, drug delivery and bioimaging. 30,[36][37][38] To date, CNCs have been used as a reinforcing component in hydrogels 5 (primarily polyacrylamide-based materials [39][40][41] ) and other biocomposite materials including electrospun poly(lactic acid) 42 and cellulose fiber scaffolds.…”

Design and Synthesis of Fluorescent Nanocelluloses for Sensing and Bioimaging Applications

“…The fact that the cell nucleus is dark suggests that CNCs indicator has little interaction with the nucleus. Good cell membrane penetration and non‐cytotoxicity make them useful in fluorescent bioimaging and drug delivery …”

“…In addition, the specific orientation of probe within bones is caused by chemical interaction between Ca 2+ and negative charge of CNC surface. Therefore, CNCs as a potential nano device can be developed for the treatment of bone tumors …”

“…Good cell membrane penetration and non-cytotoxicity make them useful in fluorescent bioimaging and drug delivery. [89,90,91,92,93,94] In addition to the cellulose nanocrystals used above, in 2018, Nei et al have developed an efficient labeling scaffold by using the cellulose-binding domain of Cellulomonas fimi CenA protein combined with pH-sensitive enhanced cyan fluorescent protein (CBD-ECFP) to achieve measurement of pH and Ca 2 + gradients by fluorescence intensity and lifetime imaging. The results demonstrated that CBD-ECPF has excellent pH sensitivity comparable to untagged ECFP (1.9-2.3 ns for pH [6][7][8].…”

Nanocrystalline Cellulose-Assisted Generation of Silver Nanoparticles for Nonenzymatic Glucose Detection and Antibacterial Agent

“…Nanocrystalline cellulose (NCC) refers to the nanorod-like cellulose of 100-300 nm in length generated by removing the amorphous part of cellulose materials from forest and agricultural crops via hydrolysis or oxidation. [1][2][3][4][5] NCC has the merits typically associated with nanorod materials, including large surface area, high specific strength, and unique optical properties. In addition, NCC possesses the following distinct characteristics: (1) NCC is a kind of green material, which is renewable and biodegradable.…”