Multi-functional vesicles for cancer therapy: The ultimate magic bullet

Delivering chemotherapy specifically, effectively and safely to tumor remains a significant challenge in recent years. Although cancer cells are more vulnerable than normal to the effect of anticancer agents, these drugs are non-selective and can cause injury to normal tissues. Different approaches i.e. passive, active and magnetic targeting, smart devices with appropriate stimuli-sensitive properties or drugs combinations, have been already proposed as single methods, contributing to minimize severe side effects and enhancing tumor-targeting efficacy. Often, the use of a single strategy is not sufficient, whereby multi-functional approach has been suggested as further evolution of traditional "magic bullet" proposed in the early 1900s by Paul Ehrlich. Among the macromolecular systems useful for targeted drug delivery, liposomes and niosomes are the most extensively studied and they own the most suitable characteristics to be converted in multi-functional devices. Liposomes and niosomes are nanovesicles that contain amphiphilic molecules arranged in concentric bilayers, delimitating an aqueous core. These vesicular carriers are very versatile, since they can be differently designed and modified in such a way that they exhibit combinations of the following properties: longevity in blood, specific target to the tumor, respond to internal/external stimuli, promotion of drug intracellular delivery. This review will focus on the potential of multi-functional vesicular nanocarriers in cancer therapy, analizing each combination of targeting strategies, stimuli-sensitivity and drug combinations and giving an exhaustive collection of recent investigations. Many multi-functional vesicular devices have shown great promise in clinical application, indicating broad potential as therapeutics in the near future, but more needs to be done. The development of more specific and efficient carriers for a personalized cancer therapy is the next challenge.