| Cancer is one of the most difficult diseases to cure.Metastases are the primary cause of death from cancer.Metastasis is not a linear cascading event,but a complex systemic event.It is widely believed that Circulating tumor cells(CTC)are the key factor to cause tumor metastasis.CTC can quickly reflect the state of disease and has a strong correlation with tumor metastasis.It is an important indicator for tumor prognosis and curative effect evaluation.However,in vivo detection of CTC is very difficult.At present,in vitro detection of CTC is mainly carried out by drawing blood in clinical practice.Since the number of CTCs is very rare,in vitro testing may cause CTCs to be lost during sample preparation and cannot be detected in real time.In this study,in vivo flow cytometry was used to realize real-time monitoring of CTC in animal tumor models,and the following work was done by using this system:Firstly,in vivo flow cytometry was used to elucide for the first time the dynamic change of CTC after Photodynamic therapy(PDT)of orthotopic breast cancer model,and it was found that PDT affects tumor metastasis through CTC.The mice were treated with PDT and resection,respectively.The changes of CTC were monitored by in vivo flow cytometry.Our results showed that compared with the tumor resection group,the light alone group and the group without any treatment,the tumor disappeared in the PDT group after treatment,and gradually recurred at the site of the primary tumor 2 weeks later,and the recurrence time of PDT group was significantly slower than that of the surgical resection group.During the whole course after PDT treatment,the CTC level remained low,and no lung or liver metastasis was observed.In contrast,metastases were found in both liver and lung in the surgical resection group.Our data analysis showed a strong correlation between CTC levels and lung and liver metastases.Thus,PDT greatly reduces transfer by CTC.Secondly,we present a new method that can safely and effectively label CTC in vivo,which is suitable for in vivo detection.Compared with normal cells,tumor cells showed significant metabolic abnormalities.Taking advantage of the characteristic of tumors,2-[N-6(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose(2-NBDG)is used to label CTC in vivo.The structure of 2-NBDG is very similar to that of Fluorodeoxyglucose(FDG)the clinical tracer for PET.It is a safe and excellent glucose analogue,which can emit strong green fluorescence when stimulated by blue light.The green fluorescence of 2-NBDG from CTCs is then noninvasively detected by an in vivo flow cytometry system.Due to the high uptake of glucose by tumor cells,the CTCs in mice can maintain a high 2-NBDG level and thus be distinguished by 2-NBDG fluorescence in vivo efficiently,enabling tumor detection in vivo like positron emission tomography(PET)but at the single-cell resolution.Our results suggest 2-NBDG,a glucose analog with high biosafety,holds promising potential in clinical applications.We investigated the way to improve the efficiency of PDT therapy,that could reduce the probability of tumor recurrence after treatment.Porphin,porphyrin and its derivatives,which are commonly used in clinical practice,will aggregate and cause energy quenching at a certain concentration,leading to the decrease of PDT efficacy.In this study,we propose a strategy to overwhelm the ACQ of porphyrin by doping it with a type of aggregation-induced emission(AIE)luminogen to produce a binary nanoparticle with high biocompatibility,and enhanced ROS generation capability.Such nanoparticle can be readily synthesized by mixing a porphyrin derivative,Chlorin E6(CE6)with a typical AIE luminogen,1,1,2,2-brominated tetrastyrene(4,4 ’,4 ’,4 ’-(ethene-1,1,2,2-tetrayltetrakis(benzene-4,1-diyl).)Tetrakis(1-(4-bromobenzyl)pyridin-1-ium)bromide,(TPE-Br).Our results have demonstrated the feasibility and effectiveness of this strategy,endowing it a great potential in clinical applications. |
