(a) Schematic of the assembly of CA-dots. Cellulose acetate is dissolved in an organic solvent and pluronic acid is dissolved in an aqueous phase to produce PEG-coated CA-dots; folate-functionalized CA-dots are assembled in a similar way. (b) Fluorescent image of CA-dots containing encapsulated Stilbene 420 (blue), Rhodamine 560 (green), Tracer Yellow (yellow), and Methylene Blue (red/NIR); fluorescence of blue, green, and yellow CA-dots were excited with UV light and the NIR dye with a red laser. (c) AFM image of CA nanoparticles, insert shows spherical geometry of the particles; (d) fluorescent image of single CA-dots near the surface of a glass slide.
(a) Schematic of the assembly of CA-dots. Cellulose acetate is dissolved in an organic solvent and pluronic acid is dissolved in an aqueous phase to produce PEG-coated CA-dots; folate-functionalized CA-dots are assembled in a similar way. (b) Fluorescent image of CA-dots containing encapsulated Stilbene 420 (blue), Rhodamine 560 (green), Tracer Yellow (yellow), and Methylene Blue (red/NIR); fluorescence of blue, green, and yellow CA-dots were excited with UV light and the NIR dye with a red laser. (c) AFM image of CA nanoparticles, insert shows spherical geometry of the particles; (d) fluorescent image of single CA-dots near the surface of a glass slide.
(f) Ex vivo mouse colon with developed colorectal cancer labeled using folate-functionalized green CA-dots. Tumor areas are easily identifiable in the bright field images of colon as green fluorescent regions.
(f) Ex vivo mouse colon with developed colorectal cancer labeled using folate-functionalized green CA-dots. Tumor areas are easily identifiable in the bright field images of colon as green fluorescent regions.

Nanoparticles made from one of the most developed and abundant biopolymers, cellulose acetate, could be promising candidate for medical imaging applications, according to new research [Peng et al., Materials Today (2018), https://doi.org/10.1016/j.mattod.2018.11.001].

The biopolymer, which is synthesized by reacting natural plant-derived cellulose with acetic anhydride, is similar to rayon and widely used in clothing and textiles, absorbency products and filters, and frames for eyeglasses. Now, however, a group of researchers led by Tufts University has synthesized a new family of cellulose acetate nanoparticles with encapsulated fluorescent molecules.

“Other optical and fluorescent materials based on cellulose acetate have been developed, but nanomaterials made of this derivative of cellulose did not exist previously,” points out Igor Sokolov, who led the effort.

The cellulose acetate nanoparticles – or CA-dots – are 50-90 nm in size and can be tuned to cover the entire optical spectrum, depending on the type of fluorescent dye used. Compared with other fluorescent particles, the CA-dots are very bright and highly stable.

“These are one of the brightest (if not the brightest) fluorescent nanoparticles,” claims Sokolov. “[As they are] fully biocompatible, [we expect them] to have promising applications in medicine and biomedical imaging.”

The nanoparticles are synthesized using a nanoprecipitation process, which involves mixing aqueous and nonaqueous phases. By controlling the surface tension at the interface between phases, particles of nano-dimensions can be produced.

“It is a technologically simple and effective process,” says Sokolov. “Our modification of this process, which concerned appropriate control of the surface tension, allows us to obtain particles of quite small size and desirable surface properties.”

As well as being fluorescent, the nanoparticles can be readily coated with different surface molecules to target specific species inside the body. As a demonstration, the researchers functionalized the CA-dots with folic acid molecules, because folic acid receptors are overexpressed in many epithelial cancers. The modified CA-dots enabled quick and easy detection of epithelial tumors as small as 10 microns in zebrafish and when applied topically to the colorectal tissue of mice.

“[CA-dots] can be used in pretty much any biomedical imaging applications [and show] unusually strong targeting of cancer,” comments Sokolov. “[They] should be interesting in any application where high brightness, low toxicity, and low cost are important.”

The team now wants to understand the mechanism underlying the unusually high brightness and the effect of different fluorescent dyes. They also hope to develop the approach to help identify precancerous colorectal lesions during routine colonoscopies, which can be easy to miss.

“At this moment, we see no shortcomings,” says Sokolov. “We also plan to develop various fluorescent sensors based on these particles and study how they work in other biomedical imaging applications.”