Near-infrared pH-switchable BODIPY photosensitizers for dual biotin/cRGD targeted photodynamic therapy

Photodynamic therapy (PDT) is a clinically-approved cancer treatment that is based on production of cytotoxic reactive oxygen species to induce cell death. However, its efficiency depends on distribution of photosensitizer (PS) and depth of light penetration through the tissues. Tendency of pathological cancer tissues to exhibit lower pH than healthy tissues inspired us to explore dual-targeted pH-activatable photosensitizers based on tunable near-infrared (NIR) boron-dipyrromethene (BODIPY) dyes. Our BODIPY PSs were designed to carry three main attributes: (i) biotin or cRGD peptide as an effective cancer cell targeting unit, (ii) amino moiety that is protonated in acidic (pH 640nm) allowed for high phototoxicity against HeLa (αvβ3 integrin and biotin receptor positive) and A549 (biotin receptor positive) cells compared to healthy MRC-5 (biotin negative) cells. Moreover, no dark toxicity was observed on selected cell lines (>10 μM) providing promising photosensitizers for tumour-targeted photodynamic therapy. [Display omitted] •Targeted and pH-switchable BODIPY photosensitizers effective against cancer cells.•Photosensitizers 4-times more active in acidic pH 5.0 than at neutral pH 7.5.•Photosensitizers showed no dark toxicity and low phototoxicity on healthy cells.