Lipid micelles packaged with semiconducting polymer dots as simultaneous MRI/photoacoustic imaging and photodynamic/photothermal dual-modal therapeutic agents for liver cancer

Abstract

Incorporating multiple imaging modalities and simultaneous therapeutic functions together into one single nano-formulation is of great importance for developing high-performance clinical-translatable theranostic agents. Herein, we fabricated multifunctional lipid-micelles incorporated with semiconducting polymer dots and a photosensitizer (referred as Pdots/Ce6@lipid-Gd-DOTA micelles) for combined magnetic resonance imaging (MRI)/photoacoustic imaging (PAI) and photodynamic (PDT)/photothermal (PTT) dual-modal therapy that induced by a single laser to achieve enhanced cancer therapeutic efficiency. The Pdots/Ce6@lipid-Gd-DOTA micelles with excellent water dispersibility were comprised of a core with poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']-dithiophene)-alt-4,7-(2,1,3-benzo-thiadiazole)] dots (Pdots) and Ce6 molecules inside, and a lipid-PEG outlayer conjugated with gadolinium-1,4,7,10-tetraacetic acid. The prepared Pdots/Ce6@lipid-Gd-DOTA micelles exhibited extremely low cytotoxicity, and had excellent MR- and PA-imaging contrast-enhancement ability, which could synchronously offer anatomical information and morphological information of tumors. Moreover, both Pdots and Ce6 photosensitizer, encapsulated inside the lipid-Gd-DOTA micelles, exhibited high NIR absorption at 670 nm and were applied to combine photothermal and photodynamic therapy simultaneously to achieve enhanced synergistic cancer therapeutic efficiency both in vitro and in vivo. In summary, our studies demonstrated that Pdots/Ce6@lipid-Gd-DOTA micelles with multi-diagnosis modalities and simultaneous dual-modal photo-therapy functions might be a potential interesting theranostic platform for tumor treatment.