Targeted drug delivery systems: synthesis and in-vitro bioactivity and apoptosis studies of gemcitabine-carbon dots conjugates

Bladder Cancer

Yunus U, et al. Biomed Mater 2020.


Gemcitabine is used to treat various cancers like breast, pancreatic, non-small lung carcinoma, ovarian, bladder and cervical cancers. Gemcitabine (GEM), however, has the problems of non-selectivity. Water-soluble, fluorescent and mono-dispersed carbon dots (CDs) were fabricated using sucrose by ultrasonic method. CDs were further conjugated with GEM through amide linkage. The physical and morphological properties of these carbon dots-gemcitabine conjugates (CDs-GEM) were determined using

different analytical techniques. In vitro cytotoxicity and apoptosis studies of CDs-GEM conjugates were evaluated by various bioactivity assays on human cell lines, MCF-7 (human breast adenocarcinoma) and HeLa (cervical cancer) cell lines. Results of kinetic studies have shown maximum drug loading efficacy of 17.0 mg of GEM per 50.0 mg of CDs. CDs were found biocompatible, and the CDs-GEM conjugates exhibited excellent bioactivity and exerted potent cytotoxicity against tumor cells with IC50 value of 19.50 μg/mL in HeLa cells which is lower than the IC50 value of pure GEM (~20.10 μg/mL). In vitro studies on CDs-GEM conjugates demonstrated the potential to replace the conventional administration of GEM. The CDs-GEM conjugates are more stable, have higher aqueous solubility and are more cytotoxic as compared to GEM alone. The CDs-GEM conjugates show reduced side effects to the normal cells along with excellent cellular uptake. Hence, CDs-GEM conjugates are more selective towards cancerous cell lines as compared to non-cancerous cells. Also, CDs-GEM conjugates successfully induced early and late apoptosis in cancer cell lines and might be effective and safe to use for in vivo applications.