Novel Approaches Aiming to Overcome Current Nanomedicine Limitations

In recent decades, a series of nanotechnology-based therapeutics and imaging agents were tested in preclinical and clinical studies relating to cancer and other pathologies. Many promising formulations were developed, aiming to increase therapeutic efficacy by exploiting the unique possibility offered by nanomedicines. Examples of important achievements, obtained by introducing these systems, include the possibility of controlling vector features, influencing interplay with biological systems, and increasing drug accumulation at the tumor site.

Some of the more promising technologies discovered were approved for clinical application, thus positively influencing the therapeutic efficacy of treatments when compared to their free drug counterparts. Despite this, some limitations related to the use of these systems still remain only partially solved. The growing interest in researching novel approaches aiming to face these challenges and to refine the formulation design could possibly impact both the efficacy and application of nanosystems.

Despite the considerable improvements made in recent years in developing efficient anticancer nanomedicines, some challenges still remain to be addressed. Finding innovative strategies to refine the use of nanoformulations is strictly necessary to fully exploit their potential.

New solutions to partially solved problems are required. This mainly applies to the negotiation of biological barriers the nanomedicines encounter during their route to the target. Crossing tumor endothelium for example, might not occur in sufficient extent, due to intrinsic features of some tumors. Diseased tissue targeting may not be completely functional, as it is limited by the formation of a protein corona on the particle’s surface, physically covering molecules deputed to targeting. Mononuclear phagocytic system uptake a considerable fraction of nanotherapeutics generating off target effects. The choice of material composing formulations designed for preclinical studies does not always respect biocompatibility, with consequent risk of toxic and/or immuno-toxic effects. Additionally, for those therapeutics relying on the cytosolic delivery of nucleic acids or other drugs, the endosomal escape is often suboptimal. Small refinements on these well recognized and characterized aspects have the potential to turn into big differences in term of therapeutic efficiency.

This Research Topic will collect original articles, reviews and a range of article types, in which authors propose novel strategies for improving nanoparticles performances. This Research Topic welcomes manuscripts addressing, but not limited to, the following themes:

• Nanotechnologies actively able to overcome the endothelial barrier or to deposit on endothelial cells and release their payload thereof.

• Nanotechnologies or strategies allowing the vectors to more efficiently escape from mononuclear phagocytic system uptake.

• Innovative disease site targeting strategies.

• Nanotechnologies presenting minimal toxicity associated to the vector itself (this also applies to immune-toxicity)

• Nanotechnologies and strategies boosting the cytosolic delivery of nucleic acids and drugs (with particular attention will be given to the cytosolic delivery of nucleic acids).