Recent advances in near infrared upconverting nanomaterials for targeted photodynamic therapy of cancer

Photodynamic therapy (PDT) is a well-established treatment of cancer that uses the toxic reactive oxygen species, including singlet oxygen (1O2), generated by photosensitiser (PS) drugs following irradiation of a specific wavelength to destroy the cancerous cells and tumours. Visible light is commonly used as the excitation source in PDT, which is not ideal for cancer treatment due to its reduced tissue penetration, and thus inefficiency to treat deep-lying tumours. Additionally, these wavelengths exhibit elevated autofluorescence background from the biological tissues which hinders optical biomedical imaging. An alternative to UV-Vis irradiation is the use of near infrared (NIR) excitation for PDT. This can be achieved using upconverting nanoparticles (UCNPs) functionalised with photosensitiser drugs where UCNPs can be used as an indirect excitation source for the activation of PS drugs yielding to the production of singlet 1O2 following NIR excitation. The use of nanoparticles for PDT is also beneficial due to their tumour targeting capability, either passively via the enhanced permeability and retention (EPR) effect or actively via stimuli-responsive targeting and ligand-mediated targeting (i.e. using recognition units that can bind specific receptors only present or overexpressed on tumour cells). Here, we review recent advances in NIR upconverting nanomaterials for PDT of cancer with a clear distinction between those reported nanoparticles that could potentially target the tumour due to accumulation via the EPR effect (passive targeting) and nanoparticle-based systems that contain targeting agents with the aim of actively target the tumour via a molecular recognition process.