Designing a lysosome targeting nanomedicine for pH-triggered enhanced phototheranostics

Abstract

Developing intelligent photosensitizers (PSs) responding to the tumor microenvironment (TME) to maximize the therapeutic efficacy and minimize side effects is a major problem for tumor phototherapy. In this paper, a dimethylamino (–NMe₂)-functionalized boron dipyrromethene (Bodipy) derivative, namely, (E)-3-(4-(dimethylamino)styryl)-5,5-difluoro-2,8-diiodo-1,7,9-trimethyl-10-phenyl-5H-di-pyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-4-ium-5-uide (BDPIN) has been designed and synthesized by a Knoevenagel condensation reaction. BDPIN has a high singlet oxygen quantum yield (¹O₂ QY) of 74.8% in dichloromethane, and retains high ¹O₂ generation ability when nanoprecipitated in water with DSPE-PEG. For the synergistic therapy (photothermal conversion efficiency ∼28.6%), BDPIN NPs show a low half maximum inhibitory concentration (IC₅₀) of 4.4 μg mL⁻¹ towards human cervical cancer cells (HeLa). However, the dark toxicity of BDPIN NPs is almost negligible even at high concentrations. NPs with lysosome targeting ability can be triggered by the low acidity for enhanced phototherapy. Furthermore, an in vivo study demonstrates that NPs are able to inhibit tumor proliferation with laser irradiation, while causing no damage to normal tissues, suggesting the high phototoxicity, low dark toxicity and outstanding biosafety of BDPIN NPs. Results provide an approach for synthesizing nanomedicine in pH-activated enhanced phototheranostics.