Facile fabrication of glutathione-responsive and photothermal nanocarriers with dendritic mesoporous silica nanoparticles for the controlled drug delivery

The synergistic treatment combining chemotherapy and hyperthermy, as a promising strategy, can improve the therapeutic efficiency of tumor therapy. The glutathione-responsive, chemotherapeutic and photothermal synergistic drug delivery systems (DDS) were developed using degradable dendritic mesoporous silica nanoparticles (DDMSNs) as carriers, camptothecin (CPT) as antitumor drug, and bovine serum albumin (BSA)/CuS as photothermal reagents (denoted as DDMSNs-CPT-CuS). BSA/CuS can prevent the premature drug release during the delivery process, and convert light energy into heat under photothermal treatment. The DDMSNs-CPT-CuS composites ranging from 100 to 200 nm had a loading capacity of 150 μg mg⁻¹ for CPT and performed excellent GSH-triggered drug release behavior under condition of pH (5.0) and glutathione (GSH, 10 mM). The photothermal conversion efficiency (η) of DDMSNs-CuS was 38.8% with 808 nm laser irradiation for 10 min (2.5 W cm⁻²). The engineered DDMSNs-CuS showed the low protein adsorption capacity (140–230 μg mg⁻¹), hemolysis rate of 5% (200 μg mL⁻¹), and weak cytotoxicity for A549 and Hela cells with a cell viability of more than 75% (50 μg mL⁻¹), indicating that the developed drug carriers displayed superior biocompatibility. There were significant differences between the cell viabilities treated with DDMSNs-CPT-CuS under NIR laser irradiation and that of without NIR laser irradiation when the loaded-CPT concentration was more than 6 μg mL⁻¹. The proposed DDMSNs-CPT-CuS exhibited well performances, such as easy preparation, low cytotoxicity and high photothermal conversion efficiency. The results illustrated that DDS can achieve the synergistic treatment of photothermal therapy and chemotherapy for tumor cells. Therefore, this work provides a promising strategy to design multi-responsive and synergistic treatment DDS, and the developed DDMSNs-CPT-CuS present great potential for tumor treatment.