The Effect of Folic Acid-Targeted Nanocarriers in Ultrasound Imaging-guided Sonodynamic Therapy of Human Cervical Carcinoma (HeLa): in vitro Study

Theranostic nanocarriers can be used simultaneously for the diagnosis and treatment of cancer. In this study, the effect of dotarem- and doxorubicin-loaded nanodroplet as a theranostic agent for ultrasound-guided and -controlled release drug delivery on HeLa cervical cancer cells was investigated.

Folic acid-targeted nanodroplets consisting of dotarm (Gd-DOTA) and doxorubicin (DOX) with alginate shells were synthesized and characterized. In this study, HeLa and L929 cell lines were used as cancer and normal cells, respectively. Intracellular uptake of nanocarriers was evaluated using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Doxorubicin release in response to ultrasound exposure and its effect on cancer treatment were investigated. Ultrasound imaging was performed to assess the ultrasound signal enhancement by nanodroplets.

The characterization results confirmed the successful synthesis of nanodroplets with desirable physicochemical properties. Cytotoxicity test showed that the synthesized nanodroplets had high biocompatibility for normal cells and induced more death in cancer cells (75.3% vs 62.1%). This effect was enhanced under ultrasound exposure (51%). The ICP-OES test showed that the uptake of Gd/DOX-loaded nanodroplets for sonicated cancer cells was approximately 1.5 times higher than that for non-sonicated cells after 12 h. The results showed that the ultrasound exposure significantly increased the doxorubicin release from nanodroplets (77.5% vs 2.1%). Also, ultrasound imaging showed that perfluorohexane nanodroplets could enhance ultrasound signal intensity.

According to the results, doxorubicin- and dotarem-loaded nanodroplets with proper diagnostic and therapeutic properties can be promising theranostic agents in ultrasound-guided and controlled drug delivery for sonodynamic therapy of cancer.