Aggregation-induced emission luminogens for in vivo molecular imaging and theranostics in cancer

Cancer is one of the most fatal diseases for decades.Aggregation-induced emission luminogens(AIEgens)have been recently used as molecular imaging or therapeutic agents in cancers,due to the advantages of large Stokes shift,high quantum yield,great biocompatibility,and strong photostability.AIEgens can specifically target different types of cancer via diverse targeting strategies.AIEgen-based fluorescence imaging,especially near-infrared imaging,demonstrated deep penetration and suitable signal-to-noise ratio,which allows reliable in vivo cancer imaging.Combined with other imaging modalities,AIEgen-based multimodal imaging could provide multidimensional cancer hallmarks from different perspectives.In addition,AIEgenbased phototherapy can be used for photodynamic therapy and photothermal therapy,which facilitate ablation of cancer cells with good biosafety and high therapeutic effects in vivo.AIEgens nanoparticles fabricated with some specific chemicals,drugs,or siRNA,could display synergistic therapeutic effects for cancers.This paper comprehensively describes the current status and future perspectives of AIEgens,which have showed a great potential for the future preclinical and clinical translation on in vivo molecular imaging and theranostics in cancer.

Impairment of autophagy promotes human conjunctival fibrosis and pterygium occurrence via enhancing the SQSTM1-NF-κB signaling pathway

Pterygium is a common ocular disease with a high recurrence rate,characterized by hyperplasia of subconjunctival fibrovascular tissue.Autophagy,an important process to maintain cellular homeostasis,participates in the pathogenic fibrosis of different organs.However,the exact role of autophagy in pterygium pathogenesis remains unknown.Here,we found that autophagic activity was decreased in human pterygium tissues compared with adjacent normal conjunctival tissues.The in vitro model of fibrosis was successfully established using human primary conjunctival fibroblasts(ConFB)treated with transforming growth factor-β1(TGF-β1),evidenced by increased fibrotic level and strong proliferative and invasive capabilities.The autophagic activity was suppressed during TGF-β1-or ultraviolet-induced fibrosis of ConFB.Activating autophagy dramatically retarded the fibrotic progress of ConFB,while blocking autophagy exacerbated this process.Furthermore,SQSTM1,the main cargo receptor of selective autophagy,was found to significantly promote the fibrosis of ConFB through activating the PKCι-NF-κB signaling pathway.Knockdown of SQSTM1,PKCι,or p65 in ConFB delayed TGF-β1-induced fibrosis.Overexpression of SQSTM1 drastically abrogated the inhibitory effect of rapamycin or serum starvation on TGF-β1-induced fibrosis.Collectively,our data suggested that autophagy impairment of human ConFB facilitates fibrosis via activating the SQSTM1-PKCι-NF-κB signaling cascades.This work was contributory to elucidating the mechanism of autophagy underlying pterygium occurrence.