Fluorescence Imaging Visualization Hydrogel Drug Delivery System And Tumor Combined Therapy Research

The release of the drug is crucial for the drug delivery system,which is directly related to the therapeutic effect of the drug.Real-time monitoring the process of drug release in vivo has the vital significance.Multispectral fluorescence imaging can effectively monitor the carrier materials,drugs or tumor cells simultaneously.It can reveal the correlation between drug release and tumor treatment in real time dynamically,which provides a research basis for the design of more efficient drug delivery system.In recent years,the combination of multiple treatment methods has played a major role and gradually occupyed a dominant position in the field of cancer treatment.In this study,the thermosensitive hydrogel of poly(s-caprolactone)-poly(ethylene glycol)-poly(s-caprolactone)(PCL-PEG-PCL)was used as a carrier.A combined chemotherapy system was established by combining the gel with a nanocarrier.In another hydrogel delivery system,a chemo-photothermal synergistic therapy system was constructed by the combination of chemotherapy drug and photothermal hydrogel modified with IR820.To reveal the relationship between drug release and tumor therapeutic effect,the drugs or carriers were tracked by multispectral fluorescence imaging,and the effect of tumor treatment was monitored by bioluminescence imaging.This project is divided into two parts.In the first part,the amphiphilic block copolymer PCL-PEG4000-PCL was used as the carrier material,and the curcumin-loaded polymer nanoparticles were constructed by thin film ultrasonic method to solve the water solubility of curcumin.The curcumin nanoparticles were loaded into PCL-PEG1000-PCL thermosensitive gels together with doxorubicin to form a dual drug delivery system.The antitumor effect of combined chemotherapy of doxorubicin and curcumin was explored by visible fluorescence imaging.The structure of the prepared nanoparticles was characterized by TEM,and the drug loading and entrapment efficiency were measured by HPLC.The rheology of the thermosensitive gel was evaluated.In vitro release experiments,in vitro cytotoxicity,the uptake of drug experiments and in vivo imaging and tumor inhibition experiments were performed on the dual drug delivery system.The experimental results demonstrated that the dual drug delivery system can effectively and sustainedly release drugs to achieve a long-lasting anti-tumor effect.In vitro cell experiments indicated that the combination of doxorubicin and curcumin can increase the permeability of cell membrane and cell nucleus as well as improve the cell intake of each other,so that it enhanced the inhibition and killing effect on tumor cells.In vivo experiments suggested that the GEL-DOX-CUR NPs system has a sustained release effect on the drugs and a long-lasting antitumor effect compared to the DOX/CUR and DOX/CUR NP groups.Moreover,the tumor suppressor effect was more pronounced and the systemic toxicity was much lower.In the second part,IR820 was connected to the PCL-PEG1000-PCL thermosensitive gel polymer to afford a photothermal effect.To combine the chemotherapy and thermal therapy,doxorubicin was used as the chemotherapy drug.The relationship between drug release and tumor treatment effect was also explored through in vivo imaging.In this experiment,IR820 was successfully connected to the PCL-PEG-PCL by the characterization of FT-IR and 'H-NMR.The rheological property of PCL-PEG-PCL-IR820 hydrogel was not affected compared to PCL-PEG-PCL hydrogel.In addition,its in vitro release behavior,in vitro cytotoxicity,and photothermal conversion efficacy were also explored.The doxorubicin-loaded GEL-IR820 was intratumorally injected into the tumor-bearing mice at room temperature,and was irradiated with 808 nm laser light at the prescribed time.The carrier degradation and drug release were monitored by the in vivo imaging system,and the growth of tumor was tracked by bioluminescence imaging system.The experimental results showed that PCL-PEG-PCL-IR820 had beneficinal photothermal conversion efficiency,and PCL-PEG-PCL-IR820 gel has a good sustained release of DOX,which can play a long-term anti-tumor effect.Both in vitro and in vivo experiments suggested that chemophotothermal synergistic cancer therapy has a stronger killing effect on tumor cells compared with single-chemotherapy or single thermal therapy.In summary,we successfully constructed two visible systems of combination chemotherapy system and chemophotothermal synergistic therapy system based on the PCL-PEG1000-PCL thermoresponsive gel as the carrier.The drug release and tumor therapy was monitored by multispectral fluorescence imaging and bioluminescence imaging.The results showed that both of the two drug delivery systems had more obvious anti-tumor effect compared with a single system.Furthermore,they can reduce the systemic toxicity caused by single drug chemotherapy.It can achieve the purpose of anti-tumor with high efficiency and low toxicity,which had important significance for the combined treatment of tumors.Multi-spectral fluorescence imaging provides a new efficient,real-time,and intuitive method for the evaluation of drug delivery systems for combination therapy of tumors.