Multifunctional nanomicelles constructed via an aggregation and de-aggregation strategy for magnetic resonance/NIR II fluorescence imaging-guided type I photodynamic therapy

Fluorescence and magnetic resonance imaging (FL/MRI) has received much attention due to their complementary characteristics. However, the simultaneous enhancement of fluorescence and MR signals plus the efficacy of the treatment is still a major challenge. To tackle this difficulty, we put forward a strategy of aggregation and de-aggregation based on luminogens with aggregation-induced emission (AIE) features. NIR II photosensitizer 4,4 '-(6,7-diphenyl-[1,2,5]thiadiazolo[3,4-g]quinoxaline-4,9-diyl)bis(N,N-diphenylaniline) (TQ-TPA) with type I reactive oxygen species (ROS) generation ability and amphiphilic 2TPE-Gd were synthesized, and both of them showed the AIE feature. During the construction of nanomicelles, hydrophobic TQ-TPA spontaneously aggregated into the core of the nanomicelles formed by 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-methoxy(polyethylene glycol)-2000 (DSPE-PEG). Meanwhile, aggregates of 2TPE (tetraphenylethylene)-Gd in aqueous solution could be de-aggregated and inserted into the interface, and formed TGdTT nanomicelles (NMs). Based on this strategy and the AIE feature, the TGdTT NMs exhibited strong NIR II fluorescence and type I ROS generation ability, and enhanced T-1 relaxivity (r(1)). Moreover, in vitro, in vivo, and pharmacokinetics results demonstrated that these nanomicelles have good biosafety and a long blood circulation time. Finally, they allowed successful realization of complementary MR/NIR II fluorescence dual-modal imaging-guided photodynamic therapy (PDT) to inhibit tumor growth. This work demonstrated that the aggregation and de-aggregation strategy of AIEgens in core-shell nanomicelles is very attractive for constructing multifunctional theranostic probes.