Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
Chem Soc Rev. 2017 Oct 30;46(21):6433-6469. doi: 10.1039/c7cs00525c.
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.
卟啉是具有光物理性质的有机杂环大环，非常适合临床光疗和癌症成像。然而，由于其在水中的溶解度差、生物利用度低、肿瘤积累和皮肤光毒性等问题，其在疾病的临床治疗中的应用受到限制。这些限制促使人们开发了超分子平台，以改善卟啉的药代动力学和肿瘤归巢性。卟啉的超分子制剂还促进了单一药物介导的更深组织光活化、扩展成像和治疗诊断多模态以及多种治疗方法的协同应用。超分子卟啉结构可以克服卟啉介导的光动力疗法（PDT）的其他限制，包括限制 PDT 仅用于浅层病变的组织穿透深度低、无法治疗缺氧肿瘤以及不完全肿瘤损伤的问题。在这篇综述中，我们讨论了卟啉的光物理性质，并概述了将其纳入超分子平台所带来的临床相关优势和挑战。具体来说，我们将解释这些平台改善被动和主动卟啉向肿瘤输送的能力的基本原理，通过卟啉 Q 带的红移、能量转移和超声动力效应实现更深组织 PDT，以及实现新的卟啉介导的治疗诊断和协同治疗能力，并结合开创性和前沿的体内研究进行举例说明。
