Theranostic Nanodots With Aggregation-induced Emission Characteristic For Targeted And Image-Guided Photodynamic Therapy Of Cholangiocarcinoma

Objective:Cholangiocarcinoma（CC）is a primary malignant tumor of the biliary tract that often occurs in the bile duct of the hepatic portal.It is difficult to diagnose at the early stage due to lack of special clinical symptoms,and majority patients lose the opportunity for radical operation.Unfortunately,due to insensitive to radiotherapy and chemotherapy,the treatment of CC remains formidable challenges to improve therapeutic effect.Photosensitizer（PS）serves as the central element of photodynamic therapy（PDT）.However,conventional PSs have some obvious drawbacks,such as lack of specificity and easy aggregation in aqueous media that limit their further application in clinics.Furthermore,the use of common nanoparticles（NPs）for PDT has typically been rendered less effective by the undesirable aggregation caused quenching（ACQ）effect,resulting in quenched fluorescence and reduced reactive oxygen species（ROS）generation that diminish the imaging quality and PDT efficacy.Methods:To overcome the ACQ effect and to enhance the overall efficacy of PDT,herein,integrinα_νβ₃-targeted organic nanodots for image-guided PDT were designed and synthesized via a simple and straightforward one-step strategy based on a red emissive aggregation-induced emission（AIE）PS.HPLC,EI-MS,electron microscopy and dynamic light scattering were used to characterize the nanoparticles;TTD encapsulation efficiency was calculated;ROS productivity of the NPs were detected;In vitro and in vivo experiments were performed to detect the targeted fluorescence imaging and photodynamic therapy of the nanodots;Characteristics and mechanism of the nanodot-mediated PDT were also investigated.Result:The obtained nanodots show bright red fluorescence and highly effective ¹O₂generation in aggregate state.Both in vitro and in vivo experiments demonstrate that the nanodots exhibit excellent tumor-targeted imaging performance,which facilitates image-guided PDT for tumor ablation in a carcinoma model.Detailed analysis reveals that the nanodot-mediated PDT is able to induce time-and concentration-dependent cell death.The use of PDT at a high PDT intensity leads to direct cell necrosis,while cell apoptosis via the mitochondria-mediated pathway is achieved under low PDT intensity.Conclusion:Our results suggest that well-designed AIE nanodots are promising for image-guided PDT applications.