Designing switchable nanosystems for medical application.

Within the last decade, nanotechnology has had a major impact on preclinical development in medicine, shaping the emerging scientific field of nanomedicine. Diverse nanomaterial platforms have been introduced as a carrier systems for the delivery of a variety of payloads (e.g. drugs, proteins, peptides, nucleic acids) but additional improvement by stimulus responsiveness would be of tremendous significance. The design of intelligent, stimuli responsive nanosystems promises to expand diagnostic and therapeutic options in medicine by making available an array of highly effective, well tolerated platforms that go beyond simple delivery of drugs or imaging agents. Controlled by internal triggers which may be characteristic for a disease or by external devices that permit tight spatiotemporal control of activity, enhancement of desired therapeutic effects and further suppression of side effects in remote organs may be possible. This review focuses on the toolbox of available internal and external switches suited for the integration into nanoscale carriers and on the clinical experience with stimuli-responsive nano-platforms. A substantial body of evidence shows that internal stimuli including pH, redox potential, enzymatic activity and temperature are suited to trigger nanosystems. For some such systems, clinical trials are in progress, but solid clinical proof of significant patient benefit will be required next. Externally controlled systems include electromagnetically-, temperature-, light-, radiation- and ultrasound triggered systems, and for certain clinical indications, such systems have already proven clinical benefit.