| Background:Cancer is one of the major diseases that threaten human health.Chemotherapy generally has problems such as low bioavailability,large toxic and side effects,easy to produce drug resistance,and poor targeting.Many tumor-related drug delivery systems appear to improve efficacy and increase safety.At present,the technical bottleneck of drug delivery system research is how to accurately deliver drugs to the lesion site to achieve controlled drug release,thereby improving the in vivo bioavailability of drugs and reducing the side effects of drugs.Liposome(Lipo),as a widely used nano drug delivery system,can improve the utilization of chemotherapeutic drugs to a certain extent,but it still has the problem of insufficient targeting and easy to be quickly cleared by the immune system.Red blood cells(RBCs)have long circulation time in vivo.It has become a good natural drug delivery carrier with many advantages such as no immunogenicity,easy access and no need for in vitro culture.In view of the advantages of Lipo’s modifiable type(loading different drugs according to demand)and RBCs(long circulation time),the RBCs-lipo combined drug delivery system constructed in this study can effectively improve tumor targeting,prolong its circulation time in vivo and reduce its clearance by liver and spleen,thereby improving its anti-tumor effect.Methods:Based on the acidic nature of the tumor microenvironment(pH<7),two kinds of Lipo,DPPC liposomes(Lipo-DPPC)and DOPE liposomes containing pHresponsive phospholipids(Lipo-DOPE)were prepared by thin film spin evaporation.The targeting and half-life of the delivery drug are regulated by the difference in the binding mode between Lipo and RBCs membrane,that is,Lipo adheres to the surface of RBCs membrane or fuses with RBCs membrane.In this study,a platelet membrane(PLM)modified Lipo(PLM-lipo)drug delivery system was also constructed.The combination of PLM-lipo and RBC-lipo delivery system can improve the blood circulation time of PLM-lipo and its enrichment in the lung,so as to achieve targeted treatment of lung cancer,effectively prevent or reduce the lung metastasis of CTCs,and prolong the survival time of tumor patients.Results:The combination of drug-loaded Lipo and RBCs can effectively enhance the life of blood circulation,reduce liver and kidney clearance,and improve the anti-tumor effect of Lipo.The results show that long blood circulation time and tumor targeting ability are the key to improving anti-tumor efficacy.Liposomes adhered to the surface of RBCs can enrich Liposomes in the lungs(passive targeting)through the principle of RBCs-hitchhiking(RH)technology,so that drugs can be enriched in the lungs;the Lipo fused with RBCs membrane will circulate in the body for a long time with RBCs and continuously release the drug in the blood,and will not be enriched in any organ within 48 h.Therefore,the combination of Lipo and RBCs can improve the bioavailability of drugs in vivo and improve tumor efficacy.In order to better increase the targeting of lung cancer and further reduce the clearance efficiency of liver and kidney to Lipo,PLM was used to modify Lipo in this study.The fusion of PLM and Lipo can significantly improve the targeting of tumors.PLM-lipo was adhered to RBCs membrane by RH technology to construct RBC-PLM-lipo,which can transfer PLMlipo to the lung due to the extrusion of capillary force when blood circulation to the lung,thereby improving the targeting of the lung.At the same time,it can also prolong the circulation time in the blood and reduce the clearance of liver and spleen to reduce the toxic and side effects on the body.Conclusion:The combination of PLM and RH technology can improve the bioavailability of the existing Lipo drug delivery system.The advantages of RBCs and PLM are given to Lipo to improve its shortcomings of insufficient targeting and short half-life.It is expected to become a new way for the treatment of lung cancer and lay a foundation for the development of autologous blood cell drug delivery technology in the clinical treatment of tumors. |
