An RBC Membrane-camouflaged Biomimetic Nanoplatform For Enhanced Chemo-photothermal Therapy Of Cervical Cancer

[Objective] Due to the untargeted release of the chemotherapy drug,the efficacy of chemotherapy is often compromised by the serious side effects to patients.Recently,the development of targeted delivery systems using nanomaterials as vehicles has provide more alternatives for chemical drug transportation.In order to improve the targeting ability of drugs,we have developed an innovative bionic targeting nanocarrier for targeted drug delivery.In addition,in order to realize the combined treatment of chemistry and light and heat,we have integrated chemotherapeutics and photosensitizers into nanocarriers to form a new type of nanoplatform(GID @ RF NPs).In summary,this combinational therapy system provides a safe,rapid and effective alternative for the treatment of cervical cancer in the future.[Methods] 1.Design and synthesize GID@RF NPs;2.The morphology of GOQD,GID and GID@RF NPs were examined with the Transmission electron microscope;3.The UV-vis absorption spectrum was measured.4.The particle size and surface Zeta potential of the sample were obtained from Zetasizer.5.FI-IR spectrum was recorded on the Spectral Infrared Spectrometer.6.Drug loading efficiency and drug release in vitro.7.MTT detection of nanocarriers for cytotoxicity and specific targeting,and in vitro antitumor efficiency of nanosystems.8.Laser confocal experiment.9.The apoptosis of HeLa cells was detected with Alexa Fluor 488 ANNEXIN V/PI apoptosis kit and flow cytometry.10.Western blotting.11.After irradiation with a near-infrared laser(808 nm/5 min),the temperature change of the tumor site was photographed with the thermal infrared camera.12 Using IVIS kinetics optical system(PerkinElmer,CA)to detect and quantify the fluorescence intensity of ICG.13.Antitumor experiments in vivo.14.Histologic sections were fixed in the formalin and embedded in paraffin.Hematoxylin and Eosin(H&E)staining was performed according to standard protocols.[Results] 1.New Bionic Nanosystem GID @ RF NPs were successfully constructed.2.With the fluorescence image,it was found that laser irradiation can significantly induce ROS production in HeLa cells treated with ICG-modified nanomaterials.3.Laser irradiation assay demonstrated a strong photothermal capability of GI@RF NPs.4.MTT assay and hemolysis assay showed that the high biosafety of GOQD and GI@RF NPs.4.GID@RF NPs enhanced drug targeting specificity and the laser irradiation improved DOX release from GID@RF NPs,which accordingly reduced the side effects of DOX to normal tissues and improved the therapeutic efficiency.5.Experiments in vitro demonstrated the significant anti-tumor ability of GID@RF NPs in vitro.6.RBCM camouflage could help nanocomposite escaping from immune clearance and extend blood circulation time.7.The experiments in vivo strongly demonstrated the powerful ability of combinational therapy for inhibiting HeLa tumor growth.With the masquerading of RBCM,GID@RF NPs with targeting ability and high specificity is a very promising nanoplatform due to the good anti-tumor capacity.8.All blood parameters obtained from mice with GID @ RF NPs administration were in the normal range of healthy mice.Meanwhile,H&E staining on the main organs of all mice demonstrated that no significant inflammation or damage was observed in all treatment groups.[Conclusion] A novel GID @ RF NPs intelligent drug delivery system was successfully constructed.GID@RF NPs provides a highly safe and effective combinational therapy for anti-cervical tumor by improving tumor targeting ability and immune escape.