Advancing porphyrin's biomedical utility via supramolecular chemistry

Porphyrins are organic heterocyclic macrocycles with photophysical properties well-suited for clinical phototherapy and cancer imaging. However, their wider application in the clinical management of disease is barred by poor aqueous solubility, bioavailability, tumour accumulation and skin phototoxicity. These limitations instigated the development of supramolecular platforms that improved porphyrin pharmacokinetics and tumour-homing. The supramolecular formulation of porphyrins also facilitates single agent-mediated deeper tissue photoactivation, extended imaging and theranostic multimodality, and synergistic application of multiple therapies. Supramolecular porphyrin structures can overcome additional limitations of porphyrin-mediated photodynamic therapy (PDT), including low depths of tissue penetration that restrict PDT to superficial lesions, inability to treat hypoxic tumours, and incomplete tumour damage. In this review, we discuss the photophysical properties of porphyrins, and overview the clinically-relevant advantages and challenges arising from their incorporation within supramolecular platforms. Specifically, fundamentals underlying the ability of these platforms to ameliorate passive and active porphyrin delivery to tumours, achieve deeper tissue PDT via red-shifted porphyrin Q-bands, energy transfer and sonodynamic effects, and enable new porphyrin-mediated theranostics and synergistic therapeutic capabilities will be explained and exemplified with seminal and cutting-edge in vivo studies.