Abstract

Responsiveness to environmental stimuli is a phenomenon that characterizes living cells and organisms and relates to fundamental principles of life. It is of great interest to understand this complicated and multifactorial mechanism, in order to build multifunctional biomaterials and devices, like drug nanocarriers. Based on this concept a number of important applications have arisen, using synthetic stimuli-responsive polymers that are exhibiting novel properties, in order to produce innovative responsive nanosystems. The nanocarriers that are able to transport bioactive molecules to the target tissues are developed based on their ability to respond to the environmental stimuli found in living cells and human body. These bio-inspired nanosystems use their endogenous responsiveness sensors, which originate from the chemistry of the biomaterials that compose them. The nature and the properties of biomaterials (lipids, polymers etc) lead to appropriate biophysical behavior and compatibility with the human organism. External stimuli, like heat, light, magnetic or electric field and ultrasounds, as well as endogenous ones, such as temperature changes, pH variations, redox potential and ionic strength differences can affect the responsiveness of a bio-inspired drug delivery nanosystem and consequently, its effectiveness. Concerning the various drug nanocarriers that can be rendered stimuli-responsive, there are several classes, including liposomes, niosomes, lipoplexes and polymersomes, micellar delivery nanosystems, dendrimers, polymer-drug and polymer-protein conjugates. The scope of this work is to review the so far extensive research that has been conducted on the area of stimuliresponsive drug delivery nanosystems and to present the journey from bench to clinic.

Keywords: Stimuli-responsive, nanocarriers, nanobiomaterials, bio-inspired, advanced drug delivery nanosystems, smart systems, nanotheranostics.

Graphical Abstract