Research On The Inhibition Of IRGD-exosomes In Vitro Proliferation Of Fibroblasts

Hypertrophic scar is a kind of fibrotic disease associated with pain and itching.It affects the life quality of patients when it develops severe symptoms due to dysfunction and even disfigurement of involved regions.The treatment of this disease is difficult,because of its high recurrence rate regardless ofdrug therapy or surgical resection.However some clinical data showed that combined application of intralesional drug injection with isotope therapy or surgical resection with radiotherapy may achieve better effects.Further more injection of some anti-tumor preparations into cicatricial lesions can also get certain effect,in spite of some systemic and regionalside effects exist which limits their clinical application in therapy of pathologic scarring.So accuratecontrol of drug action seems to be necessary to avoid these side-effects.Carrier targeting to cicatricial tissue is one of the methods to control drug mechanism,and it is worthy of deep exploration,and benefit to attain a new vehicle in scarring therapy.Exosomes is a kind of nano-particles with the size about 30-120 nm.It can be derived from cells,with the function of material encapsulation and drug carrier transport.In addition,it promotes drug diffusion and penetration in the tumor,and reduces the side effects caused by the chemotherapy.The Doxorubicin can be used to surrounddrugsin this experiment mainly due to its fluorescence that makes the drug easy to be detected.These potential advantages make the doxorubicin can be wrapped in Exosomes for the treatment of Hypertrophic scar。In this study,human renal epithelial cells(293T)were transfected with plasmid to harvest i RGD Exosomes.Doxorubicin was wrapped into i RGD Exosomes through electroporationthen treated cultured fibroblasts in vitro.Effect of i RGD-Exosomes-Doxorubicin on fibroblasts was monitored.The RNA content of i RGD-Exosomes and the efficiency of targeting fibroblasts were verified using RT-PCR and flow cytometry.The potential advantages of i RGD-Exosomes-Doxorubicin in the treatment of keloid were then explored.The results showed that i RGD-Exosomes-Doxorubicin apparently inhibited fibroblasts.Flow cytometry confirmed that the targeting efficiency of i RGD-Exosomes-Doxorubicin was significantly enhanced compared with that of Blank-Exosomes-Doxorubicin.The average particle size of exosomes was obtained though nanoparticle tracking analysis(NTA).Taken together,we preliminary concluded that i RGD-Exosomes-Doxorubicin could be efficiently taken into the via i RGD to inhibit the proliferation of fibroblasts.The i RGD-Exosomes-Doxorubicin may be used in future to treat hypertrophic scar.