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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.

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The deployment of hyperthermia-based treatments for cancer therapy has captured the attention of different researchers worldwide. In particular, the application of light-responsive nanomaterials to mediate hyperthermia has revealed promising results in several pre-clinical assays. Unlike conventional therapies, these nanostructures can display a preferential tumor accumulation and thus mediate, upon irradiation with near-infrared light, a selective hyperthermic effect with temporal resolution. Different types of nanomaterials such as those based on gold, carbon, copper, molybdenum, tungsten, iron, palladium and conjugated polymers have been used for this photothermal modality. This progress report summarizes the different strategies that have been applied so far for increasing the efficacy of the photothermal therapeutic effect mediated by nanomaterials, namely those that improve the accumulation of nanomaterials in tumors (e.g. by changing the corona composition or through the functionalization with targeting ligands), increase nanomaterials' intrinsic capacity to generate photoinduced heat (e.g. by synthesizing new nanomaterials or assembling nanostructures) or by optimizing the parameters related to the laser light used in the irradiation process (e.g. by modulating the radiation wavelength). Overall, the development of new strategies or the optimization and combination of the existing ones will surely give a major contribution for the application of nanomaterials in cancer PTT.

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Size, surface charge, and shape have a huge influence on the behavior, cellular uptake, and cytotoxic profile of nanoparticles. Herein, gold core and silica shell based nanoparticles (Au-MSSs) with spherical or rod-like shape were produced, in order to disclose the effect of the shape of nanomaterials on the cellular uptake, reactive oxygen species (ROS) production, 3D tumor spheroid penetration and cytotoxicity towards cancer cells. The Au-MSS spheres induced greater reduction of the ROS content of cancer cells and also displayed a more homogeneous distribution and penetration in 3D tumor spheroids. However, the Au-MSS rods show enhanced cellular migration and uptake in 2D cell cultures, which results in a higher drug delivering capacity. Furthermore, the Au-MSS rods displayed an enhanced cellular cytotoxicity upon laser irradiation (808 nm, 1.7 W cm-2, 10 min), where less than 10% of cells remained viable. In addition, both Au-MSSs have the potential to be used as imaging agents, which further expands their applicability as theranostic agents in the biomedical area. In summary, the obtained results show that the shape of Au-MSSs is crucial for their biological performance, which will have a great influence on their therapeutic outcome. Therefore, our findings may provide useful information for the development and design of new drug delivery systems towards a more effective therapy.