| Most of micro/nano delivery systems have no capacity for active targeting tissues at the present stage.Although nano-delivery systems could accumulate to the tumor sites by the enhanced penetration and retention(EPR)effect,they could also accumulate in the area of normal cells.Patients tend to experience powerful side effects due to the death of normal cells that surround cancer cells.Surface chemical modification could enhance the active biological targeting capacity of micro/nano delivery systems.However,how to avoid opsonization and non-specific clearance remains a challenge,and cannot completely prevent clearance and results in activation of the human complement system,which significantly limit the biomedical application of micro/nano delivery systems.Inspired by the functioning of natural cells,our studies focused on how to take full advantage of long circulation capacity of red blood cells,long blood circulation capability and tumor immune-targeting ability of leukocytes,tumor-specific targeting competence of mesenchymal stem cells.New nature cell membrane camouflaged biomimetic micro/nano delivery systems were fabricated by separating cell membranes and camouflaging them with micro/nano-particles.By camouflaging micro/nano delivery systems with natural cell membranes,the ability to avoid immune clearance capacity and maintain longer blood circulation were enhanced.Moreover,the in vivo distributions of these cell membrane camouflaged delivery systems were improved simultaneously.Red blood cell membrane camouflaged magnetic hemoglobin microparticles(RBC@Hbs)with lower serum protein biofouling were obtained by camouflaging natural protein microparticles with red blood cell membranes.RBC@Hbs were studied as an oxygen targeted delivery system.Laser scanning confocal microscopy and dynamic light scattering results showed that monodispersed RBC@Hbs with the size of 2.1 ?m were successfully prepared.Moreover,RBC@Hbs displayed red blood cell like shape and are with higher density.By using an external ultrasonic field,RBC@Hbs were autonomously propelled.In addition,the speed of RBC@Hbs rise increasingly with increasing ultrasound power.They can move at a high speed of about 113 ?m/s under an ultrasound field of 10 V and 2.15 MHz.More importantly,the RBC membrane could protect magnetic hemoglobin microparticles and decrease the serum protein biofouling,thus RBC@Hbs owned longer blood movement time.This RBC@Hbs with good oxygen binding and release capacity can be used in the field of targeted oxygen delivery.The leukocyte cell membrane camouflaged microcapsules(CLMVs),which could escape from immune phagocytosis,improve circulation in blood and target tumors,were prepared by camouflaging layer-by-layer assembled polymeric multilayer microcapsules with leukocyte cell membranes.The leukocyte membrane coating was verified by using transmission electron microscopy,quartz crystal microbalance,dynamic light scattering and confocal laser scanning microscopy.The in vivo systemic circulation time half-life of CLMVs was estimated to be 8.4 h,which further confirms that the functional components of cell membrane vesicles can prevent immune clearance In vitro cancer cell experiments and in vivo tumor targeting experiments showed that CLMVs inherited the cancer cell identification capacity of the mother leukocyte cells.After being injected intravenously via the tail vein,CLMVs were able to tune the deformability like those blood cells and accumulate around tumor cells.The natural cell membrane camouflaged polymeric multilayer capsules with the immunosuppressive and tumor-recognition functionalities of natural leukocytes provide a new biomimetic delivery platform for disease therapy.By modifying the surface of biocompatible nanogels with stem cell membrane,the core-shell structured stem cell membrane-camouflaged nanogels(SCMGs)with good blood circulation capacity,avoiding immune clearance ability and tumor targeting capability were designed and prepared.In vitro anti-cancer drug delivery results show that the concentration of DOX in cancer area is 2.7 times higher than before.Meanwhile,the blood circulation capacity was also enhanced to 3.4 times after injected into blood for 24 h,indicating the higher blood circulation ability of SCMGs.In vivo antitumor effect of drug-loaded SCMGs results showed that all of the tumors in the doxorubicin encapsulated SCMGs treated group were effectively inhibited and the tumor volume remained static.After 15 days' post-injection,the average tumor volume in experimental group was 1/5 of the control group.The integration of excellent drug encapsulation and release capacities of gelatin nanogels with the immunosuppressive and tumor-recognition functionalities of natural stem cells provides a new biomimetic delivery platform for disease therapy,and may pave the way to advance in the field of artificial cells.The biomimetic photodynamic therapy system,with prolonged blood circulation time,tumor targeting capacity,photosensitizer loading ability and near infrared upconversion competence,was constructed by fusing mesoporous-silica-encapsulated ?-Na YF4:Yb3+,Er3+ upconversion nanoparticle(UCNP)with stem-cell membranes.The resulting stem cell membrane camouflaged core-shell upconversion nanoparticles(SCNPs@m Si O2)owned good cell and blood biocompatibility,stem cell like tumortargeting capability.In vivo experiments demonstrated that this novel platform exhibited remarkable accumulation at the tumor site and avoided the cellular uptake of liver and spleen.Multiphotosensitizers(MC540 and Zn Pc)were encapsulated and simultaneously activated by a 980 nm single laser.In vitro and In vivo tumor PDT results showed higher tumor inhibition efficacy by tail intravenous administration of this new photosensitizer-loaded system.This stem-cell-membrane camouflaged upconversion nanoarchitecture provides artificial UCNPs with natural cell membranes and holds considerable promise for deep-tissue PDT cancer treatment by systemic administration.In summary,this thesis camouflaged micro/nano-vehicles with natural cell membranes.The prepared cell-membranes-camouflaged synthetic micro/nano delivery platforms own prolonged blood circulation time,better anti-immune clearance capacity and good tumor targeting ability.The membrane-coated systems successfully integrated the functions of micro/nano carriers and the nature of cell membrane.Thus,they show promising application in biomedical field. |
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