Thermo- and pH-responsive nano-in-micro particles for combinatorial drug delivery to cancer cells.

Drug combinatorial therapy has been gaining the scientific community attention as a suitable approach to increase treatments efficacy and promote cancer eradication. In this study, a new pH- and thermo- responsive carrier was developed by combining doxorubicin-loaded gold-core silica shell nanorods with salicylic acid loaded poly (lactic-co-glycolic acid) based microparticles (NIMPS). The obtained results showed that the drugs and nanorods release could be triggered by the near-infrared (NIR) laser irradiation or by the exposition to an acidic environment. The in vitro 2D cell studies showed that the NIMPS are biocompatible and easily uptaken by HeLa cells. In addition, 3D cell culture models revealed that the NIMPS administration, combined with the NIR laser irradiation, was capable of reducing the size of the HeLa spheroids up to 48%. Overall, the attained data support the application of the nano-in-micro spheres as a dual stimuli responsive drug carrier system for the local administration of combined therapies to cervical cancer cells.