Emerging targeting strategies in nanomedicine

Nanomedicine aims to improve the delivery of drugs to their targets in order to enhance their efficacy while limiting unwanted side effects. Most of the approved nanomedicines for cancer therapy so far are based on so-called passive targeting of tumors, where they take advantage of the higher permeability of tumor blood vessels to passively accumulate in the tumor tissue. At the same time, nanomedicines can be functionalized with targeting ligands (e.g., antibodies, epitopes, and peptides) to specifically recognize the targeted area by active targeting (as the “magic bullet” described by Paul Ehrlich more than a century ago).

While several nanomedicines and targeted drugs have already reached the clinical settings, their efficacy is still highly debated. Therefore, extensive research efforts are focused on identifying the factors affecting drug targeting and nanomedicine efficacy. At the same time new targeting strategies are emerging, which could provide novel solutions to overcome current barriers in drug delivery. For instance, stimuli-responsive materials may provide novel ways to target drugs in response to internally or externally applied stimuli. Recently, endogenous targeting has been described as another opportunity, where nanomedicines acquire targeting capacity upon adsorption of endogenous molecules on their surface (i.e., the nanoparticle corona).

Within this context, contributions to this thematic issue are invited, including (but not limited to) the following topics:

• novel opportunities to exploit passive targeting of drugs beyond tumors
• challenges in passive targeting and possible solutions via patient stratification
• latest advances in active targeting and the design of active targeted drug carriers (including novel types of targeting ligands, strategies to control ligand density and/or orientation, and methods to characterize the quality, heterogeneity, and active fraction of targeted nanomedicines)
• drug carriers responding to internal or externally applied stimuli to achieve spatial and temporal targeting
• novel strategies for tumor targeting or to overcome current limits in active and passive targeting (e.g., by modulating the tumor microenvironment)
• strategies to deliver nanomedicine beyond the liver (e.g., organ targeting, factors affecting nanomedicine distribution, alternative administration routes, endogenous targeting via the adsorbed nanoparticle corona)
• bioinspired targeting strategies, for instance using natural nanoparticles, viral particles, exosomes or membrane nanotechnology.

In addition to research articles and reviews, we also welcome commentaries and perspective articles to analyze constructively the current challenges and limits in drug delivery, or to highlight important unanswered questions in this field.

Submission deadline: June 30, 2024