abstract
The development of stimuli-responsive nanomedicines with tunable cargo release is gathering an increased applicability in bone regeneration and precision biomedicine. Yet, the formulation of nanocarriers that explore skeletal-specific stimuli remains remarkably challenging to materialize due to several endogenous and disease-specific barriers that must be considered during particle design stages. Such anatomo-physiological constrains ultimately hinder nanocarriers bioavailability in target bone tissues and impact the overall therapeutic outcome. This review aims to showcase and critically discuss the hurdles encountered upon responsive nanocarriers delivery in the context of skeletal diseases or tissue regeneration scenarios. Such focus is complemented with an in-depth and up-to-date analysis of advances in the development of stimuli-responsive, bone-focused delivery systems. In a holistic perspective, a deeper knowledge of human osteology combined with advances in materials functionalization via simple precision-chemistry is envisioned to incite the manufacture of stimuli-triggered nanomedicines with more realistic potential for clinical translation.
keywords
TARGETED DRUG-DELIVERY; TUMOR MICROENVIRONMENT; CATHEPSIN-K; THERMOSENSITIVE NANOPARTICLES; ANTIINFLAMMATORY PEPTIDES; MATRIX METALLOPROTEINASES; BIOLOGICAL BARRIERS; INTRACELLULAR DRUG; POLYMERIC MICELLES; CONTROLLED-RELEASE
subject category
Chemistry; Pharmacology & Pharmacy
authors
Lavrador, P; Gaspar, VM; Mano, JF
our authors
acknowledgements
The authors would like to acknowledge the support of the European Research Council grant agreement ERC-2014-ADG-669858 for project ATLAS. The authors also acknowledge the financial support by the Portuguese Foundation for Science and Technology (FCT) through a Post-doctoral grant (SFRH/BPD/119983/2016, Vitor Gaspar). The authors also acknowledge Smart Servier Medical Art (https://smart.servier.com/), for providing image vectors for Figs. 1, 4 and S1, licensed under the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/license/by/3.0/).