Nanoscale Metal−Organic Frameworks: An Emerging Versatile Tool for Next-Generation Photodynamic Therapy

Photodynamic therapy has emerged as a potent strategy for treatment of cancer due to its non-invasiveness, minimal toxicity, high spatial selectivity, and potential for combination therapies. However, self-aggregation of photosensitizers, tumour hypoxia and low penetration depth of excitation photons remain prominent challenges towards its clinical application. Nanoscale metal-organic frameworks have emerged as one of the most promising materials due to their tunable composition which allows the adjustment of optical and chemical properties by changing the metal ions or organic linkers. Due to their high porosity, they serve as carriers for photosensitizers and demonstrate high tumour accumulation rates, target specificity, and penetration depth with enhanced permeability and retention effect. This review aims to explore recent developments in nanoscale metal-organic frameworks focusing on the design strategies to enhance their effectiveness in tumour microenvironment. Specifically, we have examined the approaches to address challenges posed by hypoxic tumour environment and tissue penetration depth of the various light sources. Furthermore, this review provides insights into the targeting strategies that improve the overall efficacy through stimulus-activated release and sub-cellular internalization of photosensitizers. Finally, we discussed the on-going challenges and some future directions for harnessing their full potential as therapeutic agents for effective outcome of photodynamic therapy.