Erythrocyte Membrane-wrapped Ph Sensitive Polymeric Nanoparticles For Non-small Cell Lung Cancer Therapy

The application of nano drug delivery systems(NDDSs)may enhance the effectiveness of chemotherapeutic drugs in vivo.However,the short blood-circulating time and poor drug release profile in vivo are still two major problems with them.Hence,we here designed and prepared an RBCm-wrapped pH-sensitive polymeric pro-drug delivery system of PTX,RBCm/PGSC-PTX NPs,in order to increase the circulating time of PGSC-PTX and improve PTX release at tumor microenvironment.This study was carried out to verify our hypothesis that,the red cell membrane can ensure the long circulation time of RBCm/PGSC-PTX in the blood,and that PGSC-PTX can be sensitively degraded in the acidic environment of the tumor tissue,and release a sufficient amount of PTX to kill tumor cells.We take advantage of dynamic light scattering(DLS),high performance liquid chromatography(HPLC),ultraviolet spectrophotometer(UV),transmission electron microscopy(TEM)and other instruments and methods to carry out a series of characterizations for PGSC-PTX and RBCm/PGSC-PTX nanoparticles.The PGSC-PTX and RBCm/PGSC-PTX showed spherical morphology with average sizes about 50 nm and 100 nm,respectively.The cytotoxicity of RBCm/PGSC-PTX is considerably decreased compared with that of PGSC-PTX.PTX release from PGSC-PTX and RBCm/PGSC-PTX at pH 6.5 is remarkably higher than those at pH 7.4,respectively.The RBCm/PGSC-PTX exhibited remarkably decreased cellular uptakes by macrophages than PGSC-PTX.The area under curve within 72 h(AUC)for RBCm/PGSC-PTX is significantly higher than PGSC-PTX.The RBCm/PGSC-PTX also showed significantly(p<0.005)stronger growth-inhibiting effect on tumor than PGSC-PTX.These all results indicated that RBCm/PGSC-PTX NPs have acidic sensitivity of drug release,the characteristic of long circulation,and remarkable effect of inhibiting tumor growth.This study may be an effective strategy for realizing the real tumor targeted nano drug delivery.