Physical principles of adjuvant biophysical stimuli. HT treatment (A): The use of different type of HT source alone (alternating magnetic field (AMF) or radiofrequency (RF) or laser) causes a temperature increase reaching the maximum on the body surface that decreases while moving away from the source (Left Panel). The combined use with nanoparticles is able to concentrate the heat into target cells without heating the surrounding tissues (Right Panel). HIFU treatment (B): Thermal effect: the mechanical energy is converted into heat reaching the maximum temperature on tumor by focusing the US in a site-specific manner (Left Panel). Mechanical effect: focused ultrasound causes inertial cavitation, bubble explosion and ROS formation (Right Panel). LIPUS and SDT Treatment (C): LIPUS brings microstreaming improving membrane permeability and drugs uptake, moreover, in combination with sonosensitizer, triggers stable cavitation causing ROS generation. PDT treatment (D): The light beam excites photosensitizer electrons that, returning to the basal level, transmit the energy to nearby molecules inducing two type of reaction: (a) generation of reactive oxygen species (ROS) into the medium; (b) activation of singlet oxygen (1O2) promoting also ROS production.