[en] Nanoparticulate drug delivery systems can in principle passively target tumors. However, in order to assure an optimal drug activity, it is needed the control of the biological fate of the colloid. Thus, drug carriers should be capable of responding to physiological or physical stimuli, as well as able to enhance the delivery of active agents to targeted tissues. This involves the need for an effective drug transport into the site of action, an adequate control of the biochemical factors regulating drug release, and the maintenance of drug levels under the minimum toxic concentration. Special approaches based on stimuli-sensitive materials are expected to assure the modification of the biodistribution of loaded drugs and, thus, resulting in a more efficient pharmacotherapy. The main objective of this work is to analyze the most important approaches in the formulation of stimuli-sensitive materials for active drug targeting to the specific site of action. Stimuli-sensitive drug carriers can alter their physical properties (swelling/deswelling, disruption/aggregation, etc.) under exposure to a stimulus. This property is widely used to trigger drug release at the targeted site, but can also be utilized to accumulate the drug at the non-healthy tissue or cell before allowing its release (e.g., magnetically responsive carriers). In both cases, the systemic distribution of the drug is minimized (and, subsequently, the undesired side effects), meanwhile its therapeutic activity is enhanced. Very promising active targeting strategies involving the use of stimuli-sensitive carriers include acid-triggered drug release, hyperthermia-induced drug delivery,magnetic drug targeting, light-triggered drug release, enzyme-triggered drug release, and ultrasoundmediated delivery. The introduction of the wide variety of stimuli-sensitive strategies in clinic is expected to significantly enhance the pharmacotherapy. Even though the very promising preclinical results, the future of the strategy will depend on a better understanding of the stability, physicochemistry, toxicity, and biological fate of such kind of colloids.

[es] Las nanopartículas utilizadas en el transporte de fármacos pueden, en principio, alcanzar la masa tumoral de forma "pasiva" (estrategias de transporte pasivo). Sin embargo, para asegurar un efecto farmacológico óptimo debe controlarse el destino biológico del coloide transportador de fármacos. De esta manera, cualquier sistema de este tipo debe ser capaz de responder a estímulos fisiológicos o físicos, para así aumentar la acumulación del principio activo en el lugar de acción. Para ello, es necesario un adecuado control de los factores biomecánicos que regulan la liberación de fármaco y el mantenimiento de unas concentraciones plasmáticas dentro del margen terapéutico de la molécula activa. Ante esto, se han desarrollado materiales sensibles a estímulos que aseguran una biodistribución modificada del fármaco vehiculizado y, así, una farmacoterapia más eficiente. Entre las estrategias de transporte activo basadas en coloides sensibles a estímulos destacan el transporte activo de fármacos controlado por entornos (pHs) ácidos, hipertermia, gradientes magnéticos, luz, sistemas enzimáticos y ultrasonidos. Se espera que su introducción en clínica permita mejorar significativamente la actividad farmacológica de los principios activos. Si bien se han logrado resultados preclínicos muy prometedores, el futuro de esta estrategia depende de un