Development and Characterization of Biocompatible Cellulose-Tetraphenylethylene Hydrazone Self-Assembling Nanomicelles with Acidity-Triggered Release of Doxorubicin for Cancer Therapy

The development of anticancer diagnostic and therapeutic strategies is of crucial importance to improve efficacy and therapeutic specificity. Here, we describe the synthesis and characterization of fluorescent self-assembling nanomicelles (NMs) based on a biocompatible polysaccharide (cellulose, CE) functionalized with a tetraphenyl ethylene derivative (TPEHy) and loaded with Doxorubicin (DOX) with aggregation-induced emission (AIE) properties and pH-dependent drug release. We obtained CE-TPEHy-NMs with an average diameter of 60 ± 17 nm for unloaded NMs and 86 ± 25 nm for NMs loaded with DOX, respectively. Upon testing different conditions, we obtained an encapsulation efficiency of 86% and a loading capacity of 90%. A controlled dialysis experiment showed that the release of DOX after 48 h is minimal at pH 7.4 (11%), increasing at pH 6.5 (50%) and at its maximum at pH 4.5 (80%). The cytotoxicity of blank and loaded CE-TPEHy-NMs at increasing concentrations and different pH conditions was tested on a MG-63 human osteosarcoma cell line. Based on viability assays at pH 7.4, neither unloaded nor loaded CE-TPEHy-NMs exerted any inhibition on cell proliferation. At pH 6.5, proliferation inhibition significantly increased, confirming the pH-dependent release. We characterized and studied the performance of CE-based amphiphilic, biocompatible NMs for controlled drug release in acidic conditions, such as tumor microenvironments. Further studies are required to optimize their synthesis process and to validate their antitumoral properties in vivo.