Supramolecular approaches for the treatment of hypoxic regions in tumours

Abstract

Supramolecular chemistry provides a range of ‘weak’ intermolecular interactions that allow drugs and prodrugs to self-assemble. In the complex biological setting of blood and tumours, these interactions must be stable enough for efficient and selective drug delivery to the tumour site, but weak enough to allow the release of the cytotoxic load. The non-covalent nature of supramolecular interactions enables the detachment of smaller (pro)drug monomers that can penetrate cancer cells differently to the original nanoparticles. Hypoxic tumours show low oxygen levels due to poor vascularization, which poses challenges for drug delivery and generates biological resistances. Supramolecular building blocks specifically designed for hypoxic tumours offer targeted activation of prodrug self-assemblies, enhancing effectiveness against hypoxic cancer cells and hypoxic regions in tumours. This Review explores how supramolecular chemistry can improve (pro)drug delivery and activation in hypoxic tumours. Hypoxic tumours present considerable challenges in cancer treatment owing to their specific chemistry, biology and physics, which leads to resistances to conventional therapies. This Review explores innovative strategies based on supramolecular chemistry to overcome these obstacles and discusses future research directions that might help translating supramolecular approaches to the clinics.