Integration of a Copper-Containing Biohybrid (CuHARS) with Cellulose for Subsequent Degradation and Biomedical Control

Abstract

We previously described the novel synthesis of a copper high-aspect ratio structure (CuHARS) biohybrid material using cystine. While extremely stable in water, CuHARS is completely (but slowly) degradable in cellular media. Here, integration of the CuHARS into cellulose matrices was carried out to provide added control for CuHARS degradation. Synthesized CuHARS was concentrated by centrifugation and then dried. The weighed mass was re-suspended in water. CuHARS was stable in water for months without degradation. In contrast, 25 μg/mL of the CuHARS in complete cell culture media was completely degraded (slowly) in 18 days under physiological conditions. Stable integration of CuHARS into cellulose matrices was achieved through assembly by mixing cellulose micro- and nano-fibers and CuHARS in an aqueous (pulp mixture) phase, followed by drying. Additional materials were integrated to make the hybrids magnetically susceptible. The cellulose-CuHARS composite films could be transferred, weighed, and cut into usable pieces; they maintained their form after rehydration in water for at least 7 days and were compatible with cell culture studies using brain tumor (glioma) cells. These studies demonstrate utility of a CuHARS-cellulose biohybrid for applied applications including: (1) a platform for biomedical tracking and (2) integration into a 2D/3D matrix using natural products (cellulose).

Self-Assembled Metal–Organic Biohybrids (MOBs) Using Copper and Silver for Cell Studies

“…As expected, silver MOBs were more reactive and broke down faster under cell conditions compared to CuHARS, due to the nanoparticle nature of the silver biocomposites (as shown by SEM and coffee ring behaviors). In contrast, copper MOBs as synthesized here were of a high aspect ratio structure and took a number of days to fully degrade under the cell culture conditions tested here and as recently described [3]. This was reflected as well in the toxicity of CuHARS against both SH-EP 1 cells (Figure 8D) and glioma cells (Figure 8C).…”

“…Previously we described the characterization and synthesis of self-assembled biohybrids composed of copper and the amino acid dimer cystine [1,2,3]. These copper-containing biohybrids, which we have named CuHARS, have very high-aspect ratio (linear) shape, presumably due to the cystine dimer which provides spacing between coordinated copper.…”

“…CuHARS: CuHARS were synthesized and isolated as previously described [2,3], with details specific to the work presented here provided in more detail. CuHARS were synthesized using copper sulfate and cystine at 37 °C, in 25 cm 2 cell culture flasks, with multiple flasks being used to scale up the synthesis.…”

“…AgCysNPs: Silver sulfate was reduced using the same amino acid, L-cystine, as previously described in the synthesis of CuHARS [2,3]. The entire synthesis of self-assembled AgCysNPs was carried out in 24-well cell suspension plates (VWR).…”

“…Bottom-up self-assembly of nanomaterials in general has the advantage of scalability for a given product, with the concept being that once synthesis conditions have been defined, for the case of liquid systems, the volume of the synthesis production may be increased to give a greater yield. We have utilized this concept to translate our discovery of copper-containing high-aspect ratio structures (CuHARS) into methods for characterization and concentration of the materials [1,2,3]. Using the same biological conditions carried out to generate CuHARS, we show here that silver nanoparticles capped with the amino acid dimer cystine may also be produced, consistent with the growing literature providing evidence for many silver nanoparticle capping/reducing agents including ascorbic acid, polysaccharides, and lactic acid bacteria [4,5,6].…”