Dual pH and ultrasound responsive curcumin loaded g-C3N4/Ba(OH)2 nanocarrier for chemo-photodynamic therapy

Abstract

Curcumin (Cur)-loaded graphitic carbon nitride/barium hydroxide (g-C₃N₄/Ba(OH)₂) nanocarriers (GCNB NCRs) were synthesized using a chemical precipitation method and were proved to be an effective drug delivery vehicle with ultrasound and pH sensitivity. The highest drug encapsulation efficiency of 85% was found in the GCNB nanocarrier, and upon the incorporation of polyvinylpyrrolidone (1 mg mL⁻¹) into the nanocarrier, the encapsulation efficiency was found to be 80%. After ultrasound treatment, the curcumin drug release from the folic acid (FA)-GCNB nanocarrier at pH 5.4 increased from 54.86% to 88.39%. The release of the drug at this pH occurs gradually over an extended duration of 72 h compared to the release observed in studies conducted at pH values of 1.5 and 7.4. The cell viability at 1000 μg mL⁻¹ concentration for different drug-loaded NCs under light irradiation is as follows: CUR/FA-GCNB-PVP: 25.00%, curcumin: 9.81%, Cur (5 mg)/FA-GCNB: 18.58%, and Cur (10 mg)/FA-GCNB: 15.86%, whereas that under dark conditions is as follows: CUR/FA-GCNB-PVP: 32.05%, curcumin: 17.50%, Cur (5 mg)/FA-GCNB: 25.90%, and Cur (10 mg)/FA-GCNB: 23.20%. IC₅₀ values of Cur (5 mg)/FA-GCNB and Cur (10 mg)/FA-GCNB correspond to 154.62 and 128.96 μg mL⁻¹, respectively, for the MCF-7 cell line treated under light conditions. Moreover, Cur (5 mg)/FA-GCNB and Cur (10 mg)/FA-GCNB showed IC₅₀ values of 181.11 and 165.02 μg mL⁻¹, respectively, under dark conditions. The eradication of tumor cells is accomplished by inducing the production of reactive oxygen species (ROS), as confirmed by 2′-7′-dichlorodihydrofluorescein diacetate (DCFH-DA), 1,3-diphenylisobenzofuran (DPBF) and EPR studies. A cytotoxicity study against the HEK-293 cell line confirmed the nontoxicity of the nanocomposite.