Cancer treatment is one of the prospective uses of nanotechnology [1]. Natural polymers have over the past decades been thoroughly examined for use in drug delivery, in regard to their biocompatibility and biodegradability, and their potential to deliver drugs and genes to targeted organs [2, 3]. Exosomes as a promising nanocarriers for drug delivery could be made of various kinds of biomolecule such as proteins, carbohydrates, lipids, and nucleic acids [4]. Exosomes can present improved blood stability, enabling them to move long distances under both physiological and pathological conditions inside the body. Moreover, having a hydrophilic core renders exosomes favorable to host water-soluble drugs [5].
An anti-metabolite, 5-Fluorouracil (5-FU) exhibits broad-spectrum anti-cancer activity against solid tumors [6]. 5-FU, a pyrimidine analog, is an exclusively ‘S-phase’ active chemotherapeutic agent and acting as a thymidylate synthase inhibitor and thus impeding DNA synthesis [7]. Over the last forty years, 5-FU has been exploited against cancers like colon cancer, playing practically the role as a thymidylate synthase inhibitor. However, drug resistance remains a major obstacle in the clinical application of 5-FU [8]. Apart from its limited clinical uses, it is vital to develop effective carriers to enhance 5-FU delivery, leading to better anticancer efficacy [9].
There has been great effort on developing an efficient cellulose carrier system to control the drug concentration and release rate. Bacterial cellulose (BC) has drawn considerable attention in medical, pharmaceutical, and other related areas due to biocompatibility and non-toxicity besides physicochemical properties such as its intrinsic physical, mechanical, and biological qualities [10]. Cellulose can be produced by various acetic acids producing bacterial strains of the genera Acetobacter, Gluconobacter, Gluconacetobacter and Komagateibacter. [11]. Recently, BC has attracted special consideration in biomedical applications because the polymer is nontoxic, biocompatible, moldable, and transparent [12]. Moreover, its high-porosity geometry and hydrophilic structure facilitate the absorption and carrying of high quantities of liquid drug for the polymer. This is vital in wound dressing and tissue engineering [13]. BC has been thoroughly examined for medical applications; still, rather little effort has been detailed in cancer treatment. Regarding its physicochemical features and efficiency in developing composite materials, the research focus is turning to extending the role of BC in cancer treatment [14, 15]. In the other hand, exosomes (Exo), the endogenous nanocarriers that can deliver biological information between cells, were recently introduced as a new kind of drug delivery system [16].
Regarding the potential of BC and Exo to sustained drug release, in the present study, the combination of bacterial cellulose (BC) and exosome (Exo) was prepared as a nanocarrier for prolonged release of 5-Flurouracil (5-FU). The characterization was performed using field emission scanning electron microscopy (FESEM), Differential Scanning Calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and X-ray Diffraction (XRD) techniques. After that, the drug release and the release mechanism were examined and the results were compared to 5-FU and 5-FU@BC. To confirm of improvement effectiveness, the cytotoxicity of nanocarriers containing 5-FU against colon cancer cell line, HT-29 was evaluated.