Construction And Application Of Drug Delivery System Based On Heparinized Carbon Quantum Dots

The combination of nanotechnology and biomedicine provides new ideas for building nano-drug delivery systems,achieving early diagnosis of cancer,and improving drug targeting and long-term effectiveness.Traditional chemotherapy has the disadvantages of poor specificity,large toxic and side effects,and easy formation of thrombosis,while nano-drugs can enhance drug aggregation at the tumor site and achieve slow-release and targeted therapy.Carbon quantum dots(CDs)have the characteristics of small size,easy modification,soluble in water,stable fluorescence,low toxicity,etc.In this thesis,CDs are used as drug carriers to construct two dual-response nano-drug delivery systems,which have good biocompatibility.At the same time,it achieves the effects of drug-controlled release,anti-metastatic and anti-thrombotic,and also realizes the visual tracking of drugs.The specific research contents are as follows:(1)Using glucose,ethylene glycol,and polyethyleneimine as raw materials,a simple hydrothermal method is used to prepare green fluorescent CDs.The CDs have a particle size of about 3.9 nm,a positively charged surface,and are rich in amino groups.It has good stability and good biocompatibility,can be used for bioimaging and drug delivery to achieve tracking and treatment of cancer cells.(2)The introduction of hyaluronic acid(HA)with high affinity to the CD44 receptor overexpressed on the surface of cancer cells has constructed a CDsHA/DOX drug delivery system with good targeting.The load performance of the system is good,with a maximum drug loading rate of 57%.The results of in vitro release experiments show that when HAase is present and the acidic environment is satisfied at the same time,a large amount of drug will be released,with a release rate of 53%.It is a dual-response drug delivery system with good stability.At a total of 24 hours of incubation,the system’s inhibitory effect on MGC-803 cells is about twice that of GES;when extended to 48 hours,the inhibitory effect is up to about 3 times,and the survival rate of GES cells is free doxorubicin(DOX)twice.(3)For the common thrombosis and other complications of chemotherapy,based on the CDs-HA/DOX system,anticoagulant heparin(Hep)was introduced for adjuvant therapy,and a CDs-HA-Hep/DOX drug that can effectively inhibit the growth and migration of cancer cells delivery system.The load performance of the system is good,with a maximum drug loading rate of 65%.The hemolysis rate of the system can be reduced to 1.1%,with high biocompatibility and anticoagulation function.The drug release rate is 67% in the acidic environment where HAase is present,making it a more stable dual-response drug delivery system.At 24 hours of incubation,the system’s inhibitory effect on MGC-803 cells is about 2.5 times that of GES cells;when extended to 48 hours,the inhibitory effect is as high as about 3.5 times,and the cell survival rate of GES and the system after incubation is DOX 2-3 times.The treatment effect of the system is obviously improved,and the fluorescence of CDs is used to realize the visual tracking of drugs.(4)Because the close monitoring of Hep is very important,we designed a nano-fluorescent probe based on CDs that can monitor the concentration of Hep.The probe has good selectivity,high sensitivity and high actual sample recovery rate.Its monitoring range is 0-16 U/m L,linearity is 0.98,detection limit is0.00007 U/m L,and recovery rate is as high as 96%-99%.