A novel multifunctional NCQDs-based injectable self-crosslinking and in situ forming hydrogel as an innovative stimuli responsive smart drug delivery system for cancer therapy

Abstract

In this work, we offer an easy approach to develop a novel injectable, pH sensitive and in situ smart drug delivery system for use in cancer treatments. The developed hydrogels containing nitrogen doped carbon quantum dots (NCQD), doxorubicin (Dox) and hydroxyapatite (HA) were obtained by in situ self-crosslinking. Characterization of the synthesized nanomaterials, interactions between NCQD/Dox/HA hydrogel structure were carried out by TEM, FESEM, EDS, FTIR, XPS, XRD, Zeta potential, DLS, UV-Vis, SEM, gelation time, injectability and DIST measurements. In addition, antibacterial evaluation which was performed against Staphylococcus aureus realized that HA compound significantly increased the antibacterial activity of the hybrid hydrogel. The anticancer drug release to the tumor cell microenvironment with a pH of 5.5 was found to be higher compared to the release in the normal physiological range of pH 6.5 and 7.4. MTT and live/dead assays were also performed using L929 fibroblastic cell lines to investigate the cytotoxic behavior of NCQDs, and NCQDs/Dox/HA hydrogels. Furthermore, the NCQDs/Dox/HA hydrogel could transport Dox within a MCF-7 cancerous cell at specifically acidic pH. Additionally, imaging of cell line was observed using NCQDs and their use in imaging applications and multicolor features in the living cell system were evaluated. The overall study showed that in situ formed NCQDs/ Dox/HA hydrogel represented a novel and multifunctional smart injectable controlled-release drug delivery system with great potential, which may be considered as an attractive minimal invasive smart material for future intelligent delivery of chemotherapeutic drug and disease therapy applications.