Peptides can act as targeting molecules, analogously to oligonucleotide aptamers and antibodies. They are particularly efficient in terms of production and stability in physiological environments; in recent years, they have been increasingly studied as targeting agents for several diseases, from tumors to central nervous system disorders, also thanks to the ability of some of them to cross the blood–brain barrier. In this review, we will describe the techniques employed for their experimental and in silico design, as well as their possible applications. We will also discuss advancements in their formulation and chemical modifications that make them even more stable and effective. Finally, we will discuss how their use could effectively help to overcome various physiological problems and improve existing treatments.

GALC-loaded nanoparticles can reinstate enzymatic activity in the brain of the mouse model of Krabbe disease.

Photothermal therapy (PTT) is a promising (co)treatment with translation potentiality in oncology. Nowadays, the plasmonic nanoparticle-mediated photothermal effect (PT) relies on two well established NIR-responsive platforms: gold nanorods and nanoshells. Nonetheless, these nanostructures are affected by: (i) re-shaping after irradiation that prevents multiple PT treatments, and (ii) severe limitations to clinical translation due to metal persistence issues. Furthermore, evaluation of nanoparticle performance is usually accomplished in vitro or in mouse models, reducing the translational potential of the findings. Here, we report both the straightforward production of narrow-NIR-absorbing gold ultrasmall-in-nano architectures (tNAs) and their suitability as platforms for PT upon CW-irradiation at 808 nm. PT efficiency is fully assessed against 2D cell cultures and customized 3D pancreatic adenocarcinoma models. Remarkably, the morphology of the tNAs is not affected by laser irradiation, allowing for repeated PT cycles and preserving their ability to avoid long-term body persistence in excretory system organs.